Kidney disease and electrolytes in COVID-19: more than meets the eye

Abstract

COVID-19 is a global pandemic fuelled in some countries by government actions. The current issue of Clinical Kidney Journal presents 15 articles on COVID-19 and kidney disease from three continents, providing a global perspective of the impact of severe acute respiratory syndrome coronavirus 2 on electrolytes and different kidney compartments (glomeruli, tubules and vascular compartments) and presenting clinically as a syndrome of inappropriate antidiuretic hormone secretion, acute kidney injury, acute kidney disease, collapsing glomerulopathy and thrombotic microangiopathy, among others, in the context of a brand-new cardiorenal syndrome. Kidney injury may need acute dialysis that may overwhelm haemodialysis (HD) and haemofiltration capabilities. In this regard, acute peritoneal dialysis (PD) may be lifesaving. Additionally, pre-existent chronic kidney disease increases the risk of more severe COVID-19 complications. The impact of COVID-19 on PD and HD patients is also discussed, with emphasis on preventive measures. Finally, current therapeutic approaches and potential future therapeutic approaches undergoing clinical trials, such as complement targeting by eculizumab, are also presented.

Keywords: APOL1; COVID-19; Fanconi; SIADH; acute kidney injury; cardiorenal; chronic kidney disease; haemodialysis; peritoneal dialysis.

FIGURE 1

Geographical origins of COVID-19 reports in the present issue of ckj.

FIGURE 2

The contribution of governments to the expansion of the COVID-19 pandemic outside China. COVID-19 epidemiology cannot be understood without analysing government intervention. Contrary to citizens expectations, government intervention has sometimes contributed to expand the pandemic. Like China, Italy was caught off-guard. However, the Spanish government, after watching the Italian tragedy, not only failed to prepare the country for the pandemic but actively contributed to expand the disease. By 6 March 2020, Madrid hospitals were overwhelmed by COVID-19 and patients had to be moved to larger hospitals. What was the reaction of the government led by Pedro Sanchez? Promote a large demonstration on 8 March in Madrid. Government ministers spent days promoting the demonstration that they subsequently led. Several ministers became infected, one of them needing hospital admission. For weeks, the ministers had called for the 500 000 demonstrators of 2019 to show up again in 2020. Fortunately, a majority of Spanish citizens were actually paying attention to the news and ‘only’ 130 000 showed up. This was enough, on top of the usual weekend activity that the government did not prevent, to catapult Madrid to the worldwide top in terms of deaths per 100 000 persons, only recently surpassed by New York City (NYC). The government was fully aware of the danger and in the week preceeding 8 March, it had forbidden all meetings attended by medical doctors. Similar but milder patterns were repeated by other governments. France allowed local elections to proceed. Sweden and the UK were special cases, since health authorities purposely allowed the epidemic to expand to create ‘herd immunity’. In the UK this was done without making the necessary preparations for a large increase in the need for intensive care and healthcare personnel did not have access to appropriate protection in many instances. Prime Minister Johnson totally disregarded protective measures for himself and became infected. There is no need to comment on the unconventional US government intervention, as we have all seen it on the news. Despite last minute excuses by negligent governments, there was a different, successful approach around the pandemic, as illustrated by the low number of deaths in countries such as Germany, Portugal, Poland, Greece and others. Hopefully leaders of negligent governments will be prosecuted when the pandemic is over. For Madrid and NYC, all deaths included confirmed COVID-19 deaths at hospitals and suspected out-of-hospital deaths. Belgium is not shown, as they count all suspected COVID-19 deaths and those are not reported by other countries [45–48].

FIGURE 3.

COVID-19 protection made from garbage bags in a Spanish hospital. In some hospitals, management provided garbage bags for staff, while in others, healthcare workers had to find their own garbage bags. As a consequence of the lack of enough and appropriate protective clothing or masks, Spain is among the countries with the most infected and dead healthcare personnel.

FIGURE 4.

COVID-19 and the nephrologist. The nephrologist is a key figure in COVID-19. (1) Both COVID-19 patients in the general population and those with prior CKD may develop COVID-19-associated kidney injury, which may adopt different forms. Thus tubular injury may initially only reflect proximal tubular injury (Fanconi syndrome) [17] but frequently evolves to AKI with a mainly tubulointerstitial pattern of injury [19, 20]. AKI may fail to resolve, leading to acute kidney disease and, potentially, to post-COVID-19 CKD, a possibility that requires prospective follow-up. However, thrombotic microangiopathy as well as glomerular injury have also been observed [30]. Both the genetic background and comorbidities may impact on the severity of COVID-19 and on the type and severity of COVID-19-associated kidney injury. As an example, persons of West African ancestry carrying APOL1 risk alleles may develop collapsing FSGS [8]. (2) Dysfunction or injury of other organs and systems may also cause complications that require nephrological consultation as well as negatively impact on kidney injury. Frequent examples are SIADH secretion causing hyponatraemia [15], lung disease–related hypoxaemia and inflammation aggravating AKI and heart disease causing a cardiorenal syndrome [14]. In fact, COVID-19-related kidney injury may also aggravate heart failure. (3) Both the development of kidney injury in the course of COVID-19 as well as pre-existent CKD not on dialysis or on RRT by kidney transplantation (Tx), HD or PD are associated with an increased risk of death [11, 43, 44]. Thus prevention strategies should be emphasized in HD patients and also in PD patients and kidney transplant programmes should be stopped at the peak of the pandemic [39–42, 49]. (4) Current therapy is multipronged, providing antiviral approaches together with anti-inflammatory and anti-thrombotic therapies to decrease the impact of overinflammation and prevent thrombotic complications. Finally, organ support or replacement (ventilator and dialysis) may be needed. RRT is most commonly offered by different HD or haemofiltration techniques, but in low-resource environments or when service providers are overwhelmed, acute PD is an alternative [38]. (5) However, the future lies in preventing lung, heart and kidney injury to avoid organ failure. Experimental tissue protective therapies undergoing clinical trials include anti-complement strategies (e.g. eculizumab) as well as the use of sodium–glucose cotransporter-2 inhibitors (SGLT2i), which are drugs that may protect the kidneys and heart in both diabetic and non-diabetic environments [30]. Some images are taken from https://commons.wikimedia.org/wiki/File: Kidney_Nephron_Cells.png; https://commons.wikimedia.org/wiki/File: Pituitary_gland_image.png and https://commons.wikimedia.org/wiki/File: Heart_%26_Lungs.png.