The COVID-19 Epidemic: Management and Outcomes of Hemodialysis and Peritoneal Dialysis Patients in Stockholm, Sweden.

BACKGROUND: The COVID-19 outbreak has been associated with a high morbidity, mortality, and a risk of long-term sequelae, and patients with severe COVID-19 are at increased risk of acute kidney injury. CKD patients are at high risk of being exposed to COVID-19 and suffer complications and poor outcome. In Sweden, mitigation strategies did not include lockdown. During March-April of 2020, wide-spread infection occurred in Stockholm. METHODS: Management and outcomes in forty hemodialysis (HD) patients and 4 peritoneal dialysis (PD) patients, with symptomatic COVID-19 in greater Stockholm during March and April of 2020 are reported. RESULTS: Twenty-four HD patients (60%) required medical care and hospitalization, whereas 16 patients (40%) were treated at home. Nine patients died (mortality rate of 22.5%), of whom 8 were men. The median age in non-survivors (78 years) was significantly higher than in survivors (p = 0.003). The median time in dialysis (11.5 years) was also significantly longer in non-survivors (p = 0.01). C-reactive protein (CRP) at diagnosis in 7 of non-survivors (median 213 mg/L, range 86-329 mg/L) was significantly higher than the CRP in 25 survivors (median 87 mg/L, range 1-328 mg/L) (p = 0.0003). Maximum CRP also indicated poorer outcome among hospitalized patients (p = 0.0004). The gender imbalance was striking with only men dying apart from 1 elderly woman. Only 4 PD patients were hospitalized with symptomatic COVID-19. One patient died, 2 were discharged, and 1 was treated at the intensive care unit and survived. CONCLUSION: HD patients >70 years were reported with longer dialysis vintage, higher CRP, and males were at an increased risk of dying from COVID-19, whereas those <70 years seemed to have a milder disease. Mitigation strategies to reduce rates of infection in high-risk populations remain essential. Follow-up focusing on long-term prognosis for extrapulmonary manifestations is likely to be important also in dialysis patients.

Cellular and humoral response to SARS-CoV-2 vaccine BNT162b2 in adults with Chronic Kidney Disease G4/5.

The mRNA vaccines have proven to be very effective in preventing severe disease and death from SARS-CoV-2 in the general population. However, in patients with chronic kidney disease (CKD) in dialysis or with kidney transplants (KT) the vaccine responses vary, with severe breakthrough infections as a consequence. In this intervention study we investigated the magnitude and quality of the responses to mRNA vaccination administered prior to kidney replacement therapy (KRT). Twenty patients with CKD G4/5 and nine healthy controls were followed for 12 months after receiving two doses of BNT162b2 four weeks apart and a booster dose after 3-6 months. Induction of anti-Spike and anti-RBD IgG in plasma followed the same kinetics in CKD patients and controls, with a trend towards higher titers in controls. In accordance, there was no differences in the establishment of Spike-specific memory B-cells between groups. In contrast, the CKD patients showed lower levels of anti-Spike IgG in saliva and Spike-specific CD8+ T-cells in blood, possibly influencing the capacity of viral clearance which can contribute to an elevated risk of severe breakthrough infections. In conclusion, we found that CKD patients, despite having a reduced mucosal and cytotoxic immunity to BNT162b2, demonstrated a serological response in plasma similar to healthy controls. This suggests that immunization prior to RRT is efficient and motivated. (EudraCT-nr 2021-000988-68).

[COVID-19 related mortality in Swedish patients with renal replacement therapy]. / Mortaliteten hos svårt njursjuka var hög under covid 19-pandemin.

Data from the Swedish Renal Registry (SRR) show that during the period March 16, 2020 to March 15, 2021 0.4% of all renal transplant recipients and 3% of all dialysis patients died due to COVID-19 in Sweden. Of all registered deaths, 20% were attributed to COVID-19.  In the age group 50-59 years the risk ratio for COVID-19 related mortality was 16 (95% CI 6.5-38) among transplant recipients and 22 (95% CI 7.1-69) among dialysis patients, compared to the background population in the same age group. Excess mortality, compared to the five years preceding the pandemic, was 30% for transplant recipients and 8.7% for dialysis patients, compared to 7.7% for the entire Swedish population. Detailed reports were sent to SRR for 864 patients with confirmed COVID-19 infection representing 5.0% of all transplant recipients and 13% of all dialysis patients. The case fatality rate was 7.0% and 21% respectively.

[COVID-19 and kidney disease]. / Njursjukdom risk vid covid-19.

Acute kidney injury (AKI), albuminuria and hematuria are common in Covid-19 and have been shown to increase mortality. Assessment with a urinary dipstick and creatinine at admission should be completed with a urinary sediment and quantification of albuminuria if positive. SARS-Cov-2 seems to enter and infect the endothelium and kidney cells, and contributes to damage in addition to hypercoagulability, multi organ failure and hyperinflammation. Underhydration and rhabdomyolysis can contribute to acute tubular necrosis. Anti-inflammatory treatment may be considered and discussed with a nephrologist. Treatment with ACEi/ARBs should be continued if possible.

B cell-depleting therapy with rituximab or ofatumumab in immunoglobulin A nephropathy or vasculitis with nephritis.

BACKGROUND: Approximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic-nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN. The humanized anti-CD20 monoclonal antibody ofatumumab (OFAB) may be an alternative drug for patients intolerant or unresponsive to RTX, but so far there is no report on its use in IgAVN or IgAN. METHODS: We describe clinical outcomes after 17-22 months in four adult patients with biopsy-confirmed IgAVN or IgAN treated with RTX or OFAB as well as CS soon after diagnosis. All presented with nephritic-nephrotic syndrome and one had crescentic IgAN. Rebiopsy was performed in two cases. RESULTS: RTX and OFAB were well tolerated. Albuminuria was <250 mg/day in three patients at last evaluation and two regained normal renal function. In all cases, renal function improved after therapy. In one patient with severe IgA vasculitis, rebiopsy showed disappearance of subendothelial but not mesangial immune complexes. In the case with crescentic IgAN, rebiopsy after 9 months showed no active necrotic lesions. CONCLUSIONS: B cell-depleting therapy may be an alternative treatment for patients with IgAN or IgAVN and nephritic-nephrotic syndrome. A possible CS-sparing effect should be further evaluated in randomized controlled clinical trials.

A high-throughput test to detect C.E.R.A. doping in blood.

C.E.R.A., a continuous erythropoietin receptor activator, is a new third-generation erythropoiesis-stimulating agent (ESA) that has recently been linked with abuse in endurance sports. In order to combat this new form of doping, we examined an enzyme-linked immunosorbent assay (ELISA) designed to detect the presence of C.E.R.A. in serum samples. The performance of the assay was evaluated using a pilot excretion study that involved six subjects receiving C.E.R.A. Validation data demonstrated an excellent reproducibility and ensured the applicability of the assay for anti-doping purposes. To maximize the chances of detecting the drug in serum samples, we propose the use of this specific ELISA test as a high-throughput screening method, combined with a classic isoelectric focusing test as a confirmatory assay. This strategy should make C.E.R.A. abuse relatively easy to detect, thereby preventing the future use of this drug as a doping agent.