COVID and the kidney
Acute Kidney Injury
Patients admitted to hospital due to COVID-19 are at high risk of AKI due to:
Low-grade haematuria and proteinuria is common. Proteinuria should be quantified with spot urinary protein:creatinine ratio as usual.
Management of AKI is unchanged:
There was initial concern that ACE inhibitors (ACEi) and angiotensin 2 receptor blockers (ARB) medication use could increase the severity of COVID-19. However subsequent higher quality studies have shown that this is NOT the case, and use of ACEi/ARBs should continue as normal.
For patients well enough to be managed at home they should continue their usual medication unless there is concern regarding hypovolaemia or hypotension.
On admission to hospital continuation should be considered in the context of their current blood pressure, serum potassium, AKI risk and drug indication. Clinicians should have a lower threshold to discontinue ACEi if indication is hypertension only, and higher threshold indication of heart failure with reduced ejection fraction in which discontinuation increases likelihood of decompensation.
Impact on dialysis & renal transplant patients
Below we outline the principles of managing COVID-19 in transplant patients, but given guidelines are frequently updated as new evidence emerges please see the Renal association guidelines for up to date advice.
Low threshold to swab test should be maintained as:
Dialysis patients have a high risk of morbidity and mortality from COVID-19
Dialysis patients present atypically, with less fever and cough than general population
Haemodialysis patients unable to self-isolate as must attend unit on average three times per week, so higher exposure risk
Mortality upon infection is roughly 20-25% (often an older and co-morbid population).
Additional management concerns:
Inform renal team and dialysis unit of admission; suspected or confirmed coronavirus infection will affect dialysis isolation room availability and patient transportation, so the sooner they know the better
Renal team to arrange additional ultrafiltration if concerns regarding pulmonary oedema, to help oxygenation. Comparing current weight to target dry weight will be helpful.
Below we outline the principles of managing COVID-19 in transplant patients, but given guidelines are frequently updated as new evidence emerges please see the British Transplant Society guidelines for up to date advice.
COVID-19 has a higher mortality in transplant patients than in the general population, which varies with age and comorbidities as would be suspected.
Expert consensus is to not reduce immunosuppression pre-emptively given the increased risk of graft rejection, but instead alter medications upon becoming coronavirus positive.
As ever, always discuss altering immunosuppression with patients’ renal team, as advice will vary depending on the individual patient risk profile.
Macrolides (eg. clarithromycin) and fluconazole will greatly increase CNI levels and ideally should be avoided.
Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. The Lancet Respiratory Medicine. 2020 May 14.
Sparks MA, Hiremath S et al. "The Coronavirus Conundrum: ACE2 and Hypertension Edition” NephJC http://www.nephjc.com/news/covidace2 accessed 20/8/20
Maggiore U, Abramowicz D, Crespo M, Mariat C, Mjoen G, Peruzzi L, Sever MS, Oniscu GC, Hilbrands L, Watschinger B. How should I manage immunosuppression in a kidney transplant patient with COVID-19? An ERA-EDTA DESCARTES expert opinion.
Quick tip: spot urine protein:creatinine ratio (uPCR) has replaced 24 hour urine collection as first line for quantifying proteinuria.
Quick tip: albuminuria refers to albumin loss in the urine and proteinuria refers to all protein losses in the urine - so proteinuria includes albumin losses, but albuminuria does not include all potential urine protein losses in conditions such as myeloma.
Nephrotic syndrome consists of the triad of
Nephrotic syndrome is an umbrella term for multiple conditions that lead to a leaky glomerular basement membrane. These conditions can often only be differentiated by renal biopsy but initial management of all patients with nephrotic syndrome is similar.
Patients typically present with new onset peripheral oedema. Commonly associated, though not diagnostic, features include;
Key initial investigations;
Occasionally the cause of peripheral oedema is misdiagnosed as heart failure if the serum albumin is not dramatically reduced, so all patients with “?new heart failure” should have a urine dip and urine PCR if serum albumin is low.
Clearly many hospitalised patients with a severe inflammatory response (for example due to sepsis) or decompensated liver cirrhosis will have low serum albumin and peripheral oedema, hence getting the urinalysis and urine PCR is key to diagnosis.
Notes on uPCR;
The most common mistake made is requesting the wrong test, such as ‘urine protein’ alone rather than protein:creatinine ratio.
Making the diagnosis based on the classic triad is sufficient to refer the patient to nephrology to consider further management including biopsy, but see the ‘additional work-up’ section for interest.
Quick tip; nephrotic patients are highly salt avid so may require multiple diuretics to block different portions of the nephron, in order to achieve negative fluid balance and blood pressure control.
Refer to renal if you suspect a new nephrotic syndrome and they will usually arrange urgent review to consider renal biopsy. Primary causes include minimal change disease, membranous nephropathy and focal segmental glomerulosclerosis. These are more likely if the patient does not have diabetes and has a negative myeloma screen.
If the patient has long standing diabetes (especially with diabetic complications) and has had a gradual increase in proteinuria, then this typical history is sufficient to be confident their nephrotic syndrome is secondary to diabetic nephropathy. This allows renal biopsy to be avoided in most cases, however the patient should still be referred through to renal for outpatient input.
Sometimes nephrotic syndrome is caused by secondary causes such as amyloidosis, infections, cancers and medications.
Disease on biopsy
Primary amyloidosis or secondary to chronic inflammatory response eg. rheumatoid arthritis, bronchiectasis
Minimal change disease
Hodgkin lymphoma, NSAIDs, lithium
Malignancies, SLE and other autoimmune disorders, hepatitis B and C, NSAIDs, penicillamine, infection
Focal segmental glomerulosclerosis (FSGS)
Obesity, hypertension, sickle cell disease, HIV, hepatitis C, heroin, pamidronate
Plasma cell dyscrasias, autoimmune disease, hepatitis B and C, essential cryoglobulinaemia
What additional blood tests might be helpful?
Quick tip; risk of VTE in nephrotic patients is at least 10 times higher than in the general population. Fifty percent of VTE in patients with nephrotic syndrome occurs prior to diagnosis, so consider urine dip in patients presenting with unprovoked VTE.
VTE and anticoagulation
Note that nephrotic patients are also at high risk of infection, in part due to loss of immunoglobulins and complement components in the urine.
How to help prepare patient for renal biopsy ahead of renal admission?
These indications are broadly accepted nationally and in keeping with NICE guidance, but do check local referral guidelines in case they differ.
Immediate admission from primary care via local general medical take or to renal ward;
Urgent outpatient review;
Routine outpatient review;
We have subdivided this module about pregnancy and the kidney into 4 subheadings;
Quick tip; in pregnancy it is normal for the creatinine to fall (from a mean of 60 μmol/L to a mean of 47 μmol/L). Therefore you need to be more alert to detect AKI, as a 50% increase in creatinine may still be in the ‘normal range’.
Quick tip; although fertility is often reduced in advanced CKD or dialysis, women of a childbearing age should be proactively counselled regarding contraception
All the usual causes of AKI are possible in pregnancy e.g. sepsis, hypovolemia, heart failure, acute interstitial nephritis (see AKI section) but there are a few pregnancy-specific causes of AKI to also consider.
2nd and 3rd trimesters (or postnatally):
In most cases the investigations and treatment is the same as in AKI outside pregnancy. Key tips include:
If concerned about potential aHUS contact the on-call national centre in Newcastle: www.atypicalhus.co.uk/contact-us/
It is normal to see dilation of the renal collecting system on ultrasound in late pregnancy, often more apparent on the right. Post-renal AKI is rare in pregnancy, though can be caused by uterine compression of the ureters or ureteric injury during C-section
Quick tip; Prednisolone, azathioprine, hydroxychloroquine, ciclosporin and tacrolimus are safe in pregnancy.
Women with kidney disease are likely to be on medications which require review before pregnancy, but they may inadvertently become pregnant while on them. Below advice from Wiles et al, BMC nephrology 2019.