Neutrophil gelatinase-associated lipocalin and end-stage renal disease: it is not all about the kidneys!

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is a powerful biomarker for the early detection of acute kidney injury. However, recent data suggest that NGAL also plays an important role in chronic kidney disease (CKD), reflecting the level of acute kidney damage within the CKD condition. To study whether elevated NGAL levels in CKD are a consequence of damaged tubular cells or rather due to extrarenal production, we investigated NGAL levels in anephric patients on dialysis. METHODS: Plasma NGAL levels were investigated in 14 dialysis patients who underwent bilateral nephrectomy (anephric group), 18 anuric dialysis patients with remaining kidneys (dialysis group) and 12 healthy patients (healthy group). RESULTS: Plasma NGAL levels were significantly lower in the healthy group compared with the anephric group (143 vs. 981 ng/mL; P < 0·001) or the dialysis group (143 vs. 838 ng/mL; P < 0·001), respectively. However, NGAL levels did not differ between the anephric group and the dialysis group (981 vs. 838 ng/mL; P = 0·19). DISCUSSION: Assuming that NGAL is highly expressed in chronically damaged kidneys due to tubular stress, there should be significantly less NGAL in anephric patients compared with anuric dialysis patients with remaining kidneys. In contrast to this hypothesis, we found no difference in NGAL expression between these two groups, proving the entire extrarenal NGAL production in anephric patients and suggesting that the tubular NGAL expression seems to be negligible in anuric dialysis patients.

BK virus-associated nephropathy: neutrophil gelatinase-associated lipocalin as a new diagnostic tool?

INTRODUCTION: BK nephropathy has emerged as an important cause for allograft failure in renal transplant patients. The kidney tubules are the main target of BK virus infiltration. Neutrophil gelatinase-associated lipocalin (NGAL) has been proven to be a powerful biomarker for tubular damage. Therefore, we investigated the suitability of plasma NGAL as new diagnostic tool in patients with BK infection. MATERIAL AND METHODS: We retrospectively analyzed 240 renal transplant recipients. Systematic BKV screening by plasma PCR was performed one month after transplantation and every three month thereafter for two yr. Plasma NGAL concentration was investigated using a commercial ELISA. Medical records and electronic databases were reviewed for clinical parameters. RESULTS: BK viremia (BKV+) was diagnosed in 5.0% (12/240) and BK nephropathy in 3.3% (8/240) of our patients. BKV+ patients received more induction therapy (p = 0.03) and experienced a higher rate of biopsy-proven rejections compared to 13 control patients with similar graft function but negative BKV PCR. Contrary to our hypothesis, there was no difference in plasma NGAL expression between both groups (128.6 vs. 172.2 ng/mL; p = 0.68). CONCLUSIONS: Intensified immunosuppressive therapy is associated with an increased risk for BK nephropathy. Plasma NGAL is neither suitable for diagnosing BK nephropathy nor helpful in predicting the individual course of patients with BKV infection.

Chronic kidney disease is not associated with a higher risk for mortality or acute kidney injury in transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for surgical high-risk patients with severe aortic stenosis (AS). Many of these patients suffer from chronic kidney disease (CKD), which substantially increases the risk for acute kidney injury (AKI), need for renal replacement therapy (RRT) and mortality after surgical aortic valve repair. The impact of pre-existing CKD for the outcome of TAVI is still unclear. METHODS: We retrospectively evaluated 199 consecutive patients with symptomatic high-grade AS undergoing TAVI with the CoreValve prosthesis at our centre. We analysed incidence and predictive factors for AKI, RRT and mortality in patients with and without CKD (defined as an estimated glomerular filtration rate <60 mL/min). RESULTS: 26.8% of the patients suffered from AKI, 4.9% needed RRT and 5.5% died. All patients on chronic haemodialysis (n = 10) survived. There were no significant differences between patients with or without CKD concerning the incidence of AKI, RRT and mortality. Age, peripheral vascular disease and the need for blood transfusion were independently associated with AKI. AKI proved to be a predictive factor for mortality. CONCLUSIONS: Transcatheter aortic valve replacement with the CoreValve prosthesis does not seem to bear an increased risk for patients with CKD. For surgical high-risk patients with severe AS, a more liberal consideration for TAVI as an alternative to open surgery might be justified.

Transcatheter aortic valve implantation in dialysis patients.

BACKGROUND/AIMS: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for high-risk patients. However, dialysis patients were excluded from all previous studies. The aim of this study is to compare the outcomes of TAVI for dialysis patients with those for patients with chronic kidney disease (CKD) stages 3 and 4 and to compare TAVI with open surgery in dialysis patients. METHODS: Part I: comparison of 10 patients on chronic hemodialysis with 116 patients with non-dialysis-dependent CKD undergoing TAVI. Part II: comparison of transcatheter (n = 15) with open surgical (n = 24) aortic valve replacement in dialysis patients. RESULTS: Part I: dialysis patients were significantly younger (72.3 vs. 82.0 years; p < 0.01). Hospital stay was significantly longer in dialysis patients (21.8 vs. 12.1 days; p = 0.01). Overall 30-day mortality was 3.17%, with no deaths among dialysis patients. Six-month survival rates were similar (log-rank p = 0.935). Part II: patient age was comparable (66.5 vs. 69.5 years; p = 0.42). Patients in the surgical group tended to stay longer in hospital than TAVI patients (29.5 vs. 22.5 days; p = 0.35). CONCLUSION: TAVI is a safe procedure in patients on chronic hemodialysis. Until new data become available, we find no compelling reason to refuse these patients TAVI.

Diminished Short- and Long-Term Antibody Response after SARS-CoV-2 Vaccination in Hemodialysis Patients.

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Antibody response to mRNA SARS-CoV-2 vaccines in haemodialysis patients.

BACKGROUND: Some studies have shown an attenuated immune response in haemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large population of haemodialysis patients from different outpatient dialysis centres. METHODS: We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) 3-6 weeks after the second mRNA vaccine dose in 179 maintenance haemodialysis and 70 non-dialysis patients (control cohort). Differences in anti-SARS-CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous coronavirus disease 2019 (COVID-19) infection, systemic immunosuppressive therapy and time on dialysis. RESULTS: We found a favourable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison with a non-dialysis cohort (median 253.5 versus 1756 U/mL, P < 0.001). In multivariate analysis, previous COVID-19 infection (P < 0.001) and female gender were associated with a significantly higher vaccine response (P = 0.006) in haemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (P < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in haemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection. CONCLUSION: We strongly argue in favour of regular antibody testing after COVID-19 vaccination in haemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.