Nephrologists on Lessons Learned With Kidney Disease in COVID-19

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APRIL 08, 2020 -- As rates of new cases of COVID-19 show some encouraging signs of slowing in the hardest-hit countries of Spain and Italy, nephrologists in those and other badly affected places are sharing insights and experiences learned during the pandemic.  

Although lung damage is the main feature of severe COVID-19, it is becoming crystal clear that the kidney is one of the other major organs involved, explained Annette Bruchfeld, MD, PhD, a professor of nephrology at Karolinska University Hospital in Sweden, during a webinar organized last week by the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA).

Bruchfeld discussed results from the first wave of the outbreak in China, illustrating how kidney disease on admission or which develops during infection is a major complication of severe COVID-19 and a significant risk factor in death.

Meanwhile, Maria Jose Soler, MD, PhD, a nephrologist with the Vall d'Hebron University Hospital in Barcelona, Spain, provided a snapshot of COVID-19 among kidney dialysis and transplant patients from a Spanish Society of Nephrology registry. As of April 7, this included more than 600 patients, with mortality rates ranging from 17%-23% depending on whether they were transplant or dialysis patients.

"The mortality we're seeing with these [dialysis and transplant] patients is because COVID-19 pneumonia/disease can be very aggressive with a severe distress syndrome," Soler told Medscape Medical News.

She outlined how her team had tried various pharmacological interventions in their dialysis and transplant patients while acknowledging that proper studies are required to get definitive answers."Nephrologists hope that our patients, normally excluded from randomized controlled trials, will be...included. We need data for our patients and not just speculation."

Meanwhile, Umberto Maggiore, MD, of the Department of Nephrology, University Hospital of Parma, Italy, offered a glimmer of hope.

He reported that his team has used the gout drug colchicine, among others, in the successful treatment of two kidney transplant patients with COVID-19 who both recovered. The key, he believes, is starting treatment before patients become too sick."We have started using colchicine as an anti-inflammatory drug and we are starting a randomized controlled trial on this," he noted.

The Story So Far in China; AKI Common in Those With COVID-19

Bruchfeld spoke about a prospective single-center study of 701 patients with COVID-19 in Wuhan, China, published in Kidney International.

Of the patients in the study, 43.9% had proteinuria and 26.7% had hematuria on admission, she noted. The prevalence of elevated serum creatinine, elevated blood urea nitrogen, and estimated glomerular filtration rate < 60 mL/min/1.73m2 were 14.4%, 13.1%, and 13.1%, respectively.

And during the study period, 5.1% of patients developed acute kidney injury (AKI).

Kidney disease influenced mortality, varying from a doubling of death risk with elevated baseline serum creatinine (hazard ratio, 2.10) to an almost quadrupling with elevated baseline blood urea nitrogen (HR, 3.97).

For those with AKI, the risk of dying was almost doubled for stage 1 to more than quadrupled for stage 3.

A similar pattern was seen for proteinuria, and for hematuria, although the risks were even higher for the latter.

"Our findings show the prevalence of kidney disease on admission, and the development of acute kidney disease during hospitalization, is high and is associated with in-hospital mortality," say Yichun Cheng, MD, Department of Nephrology, Huazhong University of Science and Technology, Wuhan, China.

And in a meta-analysis of 30 studies involving 53,000 patients in China — albeit a preprint that has not been peer-reviewed — chronic kidney disease was associated with a sixfold increased risk of severe COVID-19 (odds ratio, 6.0).

This compared with an OR of 5.3 for chronic obstructive pulmonary disease and 3.2 for cerebrovascular disease, Bruchfeld reported.

Dialysis/Transplant COVID-19 Experience in Spain

Soler reported that in her Barcelona registry there are currently 405 in-center hemodialysis patients hospitalized with COVID-19, among whom there have been 94 deaths (23%).

Among 26 peritoneal dialysis patients, there have been five deaths (19%), and in 206 kidney transplant patients with COVID-19, there were 35 deaths (17%).

She also reported on treatments. The most common were hydroxychloroquine (75%), lopinavir/ritonavir (47%), steroids (15%), interferon (11%), and tocilizumab (3%).

Soler noted that although lopinavir/ritonavir showed no greater efficacy than standard care in COVID-19 in a recent randomized clinical trial, she suspects the drug combination may have a better effect if started earlier in the disease course.

With high mortality rates in that study, "one realizes that they were the really sick patients with advanced COVID-19 infection," Soler said.

"So we are giving the drug earlier on — not when they are in the ICU, but earlier."

Colchicine for Transplant Patients, Before Disease Becomes Severe?

Maggiore said that they too in Italy are trying to give their drugs of choice earlier in the disease course.

They detail their experience with two kidney transplant patients with COVID-19 in a letter to the editor published last week in the American Journal of Transplantation.

They stopped immunosuppression to promote an antiviral response, keeping steroids as the only antirejection drugs. Both patients received hydroxychloroquine 200 mg twice daily in addition to antiviral therapy.

After progressive worsening of respiratory conditions and noninvasive ventilation, the patients received colchicine as an anti-inflammatory, partly because they had no tocilizumab.

Neither patient was transferred to the ICU; both recovered.

During the webinar, Maggiore further commented on the treatment of COVID-19 with steroids, noting that although some studies suggest the drugs have no benefit and are possibly detrimental in COVID-19, he believes they may be important.

"If the respiratory patient is abruptly deteriorating over 24 hours and you don't have a bed in the ICU, I think steroids should be considered," he said.