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 At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney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 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.
PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate ...the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations.
PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients 143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS) and in 945 healthy controls.
The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91, while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73).
The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.
Introduction:
Cast nephropathy is a prevalent cause of acute kidney injury (AKI) in patients with myeloma.
Objectives:
The aim of this study is to define the outcome of a standardized supportive ...therapy for cast nephropathy.
Patients and Methods:
Retrospective analysis of the outcome of cast nephropathy in a University hospital for a period of five years. Data analysed; serum creatinine, estimated glomerular filtration rate (eGFR; mL/min/1.73 m
2
BSA) and need for dialysis. Standardized therapy with the aim of preventing/removing tubular casts; fluid administration and mannitol to increase urine flow, sodium bicarbonate to alkalize the urine and low dose steroid to reduce peritubular inflammation. Statistical analysis: Student’s t-test or the Mann-Whitney test according to data distribution. A two-tailed
P
value <0.05 was considered statistically significant. Survival curve was drawn according to Kaplan and Meier.
Results:
Twenty-seven cases were reviewed. Upon admission, mean serum creatinine was 7.1±4.9 mg/dL and mean eGFR 6±4 mL/min/1.73 m
2
BSA; 30% of patients had oligo-anuria. Diagnosis of cast nephropathy was presumptive in 23 patients, and renal biopsy proven in four. Hemodialysis was required by 10 (37%) patients, two of whom continued dialysis after discharge. At discharge, serum creatinine was 3.7±2.5 mg/dL and eGFR 20±13 mL/min/1.73 m
2
BSA (
P
=0.002), and after a median of 3.4 months, the values were 2.9±2.1 mg/dL and 35±32 mL/min/1.73 m
2
BSA, respectively. Patient survival was 60% after 24 months.
Conclusion:
Administration of fluid, mannitol, sodium bicarbonate and low-dose steroid may improve the outcome of cast nephropathy. Despite the fact that the study has many limitations, its findings could be the base for prospective controlled trials on cast nephropathy and could be useful in those countries where the expensive extracorporeal treatments are not available.
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
Etelcalcetide (ETC) is an intravenous calcimimetic approved for the management of secondary hyperparathyroidism (sHPT) in hemodialysis (HD) patients, with benefits in ...terms of reduction of FGF23 levels and prevention of progression of left ventricular hypertrophy. The label recommendation is a starting dose of 5 mg after HD, to be titrated every 4 weeks according to parathyroid hormone (PTH) and calcium levels. However, it remains unclear what dosage is best to start with and, thus, how this treatment can be implemented in a real-life setting. The aim of this study was to assess the efficacy and cost-effectiveness of ETC started at lower doses than those suggested by the manufacturer in patients with moderate sHPT.
Methods
This is a retrospective observational study comparing two different initial ETC dosing strategies, a “Low-dose approach” (LD, ETC starting dose<10 mg/week) and a “Classic approach” (CL, ETC starting dose≥10 mg/week), in terms of effects on CKD-MBD related biomarkers and costs during the first year of prescription. The study was conducted on HD patients with basal PTH between 500 and 1500 ng/l, treated with ETC for at least 3 months between 2018 and 2022 at ASST Spedali Civili di Brescia. Monthly monitoring of serum calcium, phosphorus and PTH was performed in both groups for dose adjustment.
Results
Overall, 53 patients were identified, 24 in the LD and 29 in the CL group. Both groups showed similar baseline characteristics (Table 1). Median follow-up was 52 weeks, during which 4 patients (one in the LD and three in the CL group) discontinued ETC (Table 1). At the end of follow-up, 92% of patients in the LD and 90% in the CL group achieved a decrease in PTH ≥30% compared to baseline, with median PTH levels of 282 (207 - 332) and 294 (151 – 382) ng/l, respectively (p = 0.825). Other CKD-MBD biochemical parameters were comparable between the two groups at all timepoints (Figure 1). The median of average ETC weekly doses per patient was 7.6 (6.2 – 10.2) mg in the LD and 10.6 (9.7 – 15) mg in the CL group (p<0.001). During follow-up, the median ETC dose remained stable in the LD group, while partially decreasing in the CL group (Figure 1). Use of paricalcitol was comparable in both groups. At cost analysis, the median of average ETC weekly costs per patient was €36.6 (29.6 – 50.0) in the LD and €50.5 (46.4 – 71.7) in the CL group (p<0.001). This translates into an average yearly cost per patient of €1909 and €2635 using the LD and CL approach, respectively, with a saving of €726 per patient-year in favour of the LD strategy.
Conclusion
In this retrospective study in HD patients with moderate sHPT, we showed that starting ETC at a lower dose than the one suggested by the manufacturer is as effective as the classic approach in terms of control of CKD-MBD parameters, with a significant reduction in treatment costs. Future prospective studies will be needed to validate the results in bigger cohorts, test whether these benefits can extend beyond the first year of treatment and assess the effects on FGF23 levels and other relevant clinical outcomes.
Background:
Tunneled central venous catheter (tCVCs) is a vascular access frequently employed in hemodialysis patients. Catheter-related bloodstream infections (CRBSI) are potentially ...life-threatening complications.
Methods:
We performed a retrospective survey regarding tCVCs prevalence as well as the CRBSI incidence and management within five hospitals in the Brescia province belonging to the “East Lombardy Nephrological Network”; this study was based upon 18 queries regarding the years 2020 and 2021.
Results:
The data collected refer to an overall hemodialysis population of 736 patients in 2020 and 745 patients in 2021. The prevalence of tCVCs was respectively 22.1% and 24.2% with the initial placement being performed with fluoroscopy support in 80% of the centers. CRBSI incidence was respectively 0.88 and 0.77 episodes per 1000 days of tCVC use. When the CRBI was caused by Staphylococcus Aureus (SA) or Pseudomonas, differently from the recommendation of the KDOQI guidelines, the removal or the substitution of the tCVC did not occur immediately at the time of the diagnosis of the infection but only when the specific antibiotic therapy failed. A nose swab aimed at identifying SA carriers was performed in 60% of centers. The policy regarding the referral to other specialists (infectious disease specialist and microbiologist) was heterogenous across the centers according to their specific logistics.
Conclusions:
This retrospective survey performed by the “East Lombardy Nephrological Network” within the Brescia province describes the prevalence of tCVCs use as well as the incidence and management of CRBSIs in the hemodialysis patients of this area. The clinical impact of the differences in terms of clinical approach detected compared to the KDOQI guidelines will need to be clarified ideally in prospective studies.
Abstract
Background and Aims
Efficacy of acute rejection (AR) therapy has always been evaluated based upon improvement of renal function. On the contrary, the degree of histological lesion (HL) ...regression has rarely been considered for this purpose.
The main goal of this study was to evaluate the percentage of failures in HLs regression after treatment aimed at both “subclinical” and “clinical” AR. Treatment efficacy was therefore evaluated with control renal biopsies (CBs) performed 30-60 days after anti-rejection therapy. In addition, the correlation between graft function and histological data was assessed. The results of treatment for “subclinical" and "clinical” AR were considered separately.
Method
Real-time ultrasound-guided CBs were performed in an outpatient setting using 16G tru-cut needles. The HLs considered were: interstitial inflammation (i), tubulitis (t), glomerulitis (g), arteritis (v), capillaritis (ptc). Each lesion was graded from 0 to 3 (sec Banff 2013-2017). For this study, only HLs with a score ≥2 were considered. Therapy failure was determined both by the percentage of patients (pts) with persistence of HLs and by the change of HLs score after treatment, in the control biopsies. Anti-rejection therapy varied according to AR type and severity. In patients failing AR therapy, serum creatinine was evaluated before and after the treatment.
Results
111 BCs were performed after treatment either for subclinical (n = 47) or for clinical (n = 64) AR. Before therapy, HLs (with score ≥2) present in subclinical and clinical AR were: i: 23% and 52%; t: 30% and 30%; g: 34% and 41%; ptc: 11% and 28%; v: 15% and 19%.
After therapy, in the setting of subclinical AR, HLs were still present with a range between 29% (v) and 81% (g) with stable or improved histological score. In this scenario, renal function resulted stable and satisfactory (Tab 1).
In the case of clinical AR, the persistence of histological lesions ranged from 25% (v) to 92% (g), also with stable or improved histological scores. In this case, therapy was always followed by an improvement in renal function (Tab 2).
Conclusion
After AR therapy, only the morphological data obtained with histological analysis can disclose failures of anti-rejection therapy, both in presence of subclinical and clinical AR.
The high rate of treatment failure may explain the correlation between AR and worse graft survival.
Our results could lead us to consider the need for a more aggressive anti-rejection treatment.
Control renal biopsies after AR therapy should always be considered on clinical grounds.
Figure:
Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of ...cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8‐fold excess mortality (95% CI: 1.59‐2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81‐9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97‐8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03‐6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.
What's new?
Kidney transplant recipients have increased risk of developing certain cancers, but their cancer mortality is not well documented. Here, the authors conducted a cohort study of 7373 individuals who had received a transplanted kidney. Cancer was the most common cause of death, accounting for 32% of all deaths. For all cancers combined, the transplant recipients had a 1.8‐fold excess mortality; the highest excess death risks were seen with lymphomas, kidney cancers and skin melanoma. These results suggest a need for increased cancer surveillance among transplant recipients.
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