An HIV positive woman with low eGFR

A 38 year old woman who has been on anti-retroviral therapy for 3 years is found to have a creatinine of 230 micromol/l (2.6 mg/dl).  She is taking Tenofivir, Efavirenz and cotrimoxazole and has been compliant with therapy.  She complains of recurrent dysuria and frequency, as well as intermittent fevers which do not always seem related to urinary symptoms.  She describes some vaginal discharge.

On examination she is thin but not emaciated.  She has no oedema.  Her pulse is 64, blood pressure 110/60, chest is clear, cardiovascular system normal.  She has mild non-specific abdominal tenderness but no masses.

Urine dipstick is positive for nitrites and leucocytes, blood 1+.

What type of disease process do you suspect?  What further features or investigations would you immediately seek?

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She has marked renal impairment; that creatinine corresponds to an eGFR of about 26.  She already has possible explanations for renal disease from her diagnosis of HIV and the fact that she is on anti-HIV drugs, many of which have renal side effects, including crystallization, interstitial nephritis, tubular injury.

A key observation is the bland urinary sediment, showing little protein or blood, which essentially rules out severe glomerular pathology.  HIV nephropathy is a glomerulopathy, so it is an unlikely explanation. Using the pre-renal/renal/post-renal algorithm, this makes you home in on

  • Pre-renal causes.  She doesn’t sound very dehydrated, but pre-renal causes include arterial and small vessel disease; for instance thrombotic microangiopathy can occur in HIV.
  • Interstitial or tubular causes (drugs particularly likely to be implicated; tenofivir is associated with tubular injury)
  • Obstruction

The key investigation in any patient with renal failure and urinary symptoms is renal imaging.  Ultrasound is quick, non-invasive, risk-free, and almost always first choice; it should be part of the investigation of almost any patient with unexplained new severe CKD.  It showed bilateral hydroureter and hydronephrosis without distention of the bladder.

Hope you had also written that vaginal examination is one of the things that you must do here.  She had advanced cervical cancer involving both ureters.

She also had a CD4 count of 93 despite her anti-HIV therapy, with PCR showing 5,000 copies per ml, suggesting anti-retroviral failure.  In a well-resourced setting you would consider testing for drug resistance.

Further info

Thanks to Fran Th’ng and Gavin Dreyer for this case.

Renal failure from the HIV clinic

A 32 year old man presents wtih 3 days of vomiting, nausea, and malaise.  HIV was diagnosed 6 months ago but he has not been started on ant-retroviral therapy.  He has no other significant past medical history.

He is apyrexial.  BP is 100/60 and pulse 82.  He has no oedema.  JVP is not visible when lying flat.

Urine dipstick shows 1+ protein only.  The only other investigation available is serum creatinine – 700 micromol/l (8 mg/dl).

What do you think are the main diagnostic possibilities here?  What additional key questions would you like to ask? What would your initial management be?

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Case contributed by Fran Th’Ng and Gavin Dreyer

An oedematous 15 year old

A 15 year girl presents to Queen Elizabeth Hospital Blantyre with a one-month history of facial oedema.  It is worse in the morning, slightly better at night and not associated with shortness of breath or cough.  She has been well recently, with no intercurrent illnesses.  She has never had any body swelling until noticing swelling of her feet in the last week or two. On further questioning, 6 months ago she probably had an episode of macroscopic haematuria.  She has not reached menarche.  She lives in Nkhotakota.

On examination she is slim but has marked bilateral pitting pedal oedema and facial puffiness; she probably also has ascites.  She is apyrexial.  General examination is unremarkable.  Her BP is 110/60, pulse 72.  She has reduced breath sounds and dullness to percussion at both lung bases.  Heart sounds and abdomen are normal and she has no neurological deficit.

A urine dipstick shows 4+ protein, 3+ blood.  She has a serum creatinine of 60 micromol/l (0.7 mg/dl) and a normal blood count.  Tests of liver function, serum proteins are not available.

  1. What is the differential diagnosis at this stage?
  2. Further immunological tests are not possible, nor is a renal biopsy, but what simple tests are essential to your management?

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The urine dipstick findings are strongly suggestive of ‘nephritic’ type glomerulonephritis.  In this region, post-infectious glomerulonephritis is the most likely cause, though the history here is long, and she is not hypertensive.  Other causes are certainly possible.  However …

Urine microscopy is a key test in a patient with suspected glomerulonephritis.  In her case it showed red cells, but these were of normal shape, and no casts were seen.  However Schistosoma haematobium ova were seen.

Schistosomiasis is endemic around Lake Malawi.  A positive dipstick test for blood would usually be taken to indicate current infection.  Serology for Schistosoma antibodies is of no value as previous exposure is usual.

This complicates interpretation and management significantly.  Given that her creatinine and blood pressure were normal, she was treated for Schistosomiasis and reviewed one month later.  At that review she is still oedematous and urine dipstick shows 4+ protein.  Now what do you think?

Read more in A 16 year old girl with oedema

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Case contributed by Fran Th’ng and Gavin Dreyer


 

 

 

Anaemia, heart failure and CKD (21)

This elderly man has multiple medical problems.  His main current problem is heart failure – he has moderate LV dysfunction, valvular heart disease and pulmonary hypertension.  He is seen by the Heart Failure Nurse and we have reached the point where we agree his treatment is palliative.  He gets recurrent peripheral oedema and ascites.  His renal function shows a urea of around 20 and creatinine of around 200.  At home he is able to walk with a frame from his bedroom to the living room but this makes him breathless.  He is a type 2 diabetic and also has mild memory impairment.

He has had a chronic long standing anaemia over a number of years.  This has seen his haemoglobin slide from the 10.3 down to 8.3 when last checked.   He had GI investigations and was found to have a number of polyps and an area of angiodysplasia.  He has had a couple of transfusions.  It was decided earlier this year that further investigation was not appropriate.  He is on iron so it is difficult to know how much of his anaemia is due to his renal problems.

When discharged last week it was suggested that we should contact you about erythropoietin treatment.  Improvement of his anaemia might help his heart failure a little though I suspect this would only be temporary.  He is very frail and clinic attendance might not be possible.  I would be grateful for your advice

What further information would you seek before giving your opinion?

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Current medications include: bumetanide 5mg OD, metolazone 2.5mg once weekly and insulin.

 

 

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There are 2 issues here:

1. Anaemia & EPO – the advice given to you is a bit misleading.  EPO is designed to bring haemoglobin up slowly, the recommended rise being 1gm/month.  In other words, he’s going to get decent haemoglobin in about 2-3 months time.  Furthermore, EPO is contraindicated in GI bleeding and his anaemia is probably mainly due to angiodysplasia rather than renal disease.  I would normally commit someone like this to regular transfusion.

2. Oedema – I would try and dry him out and ignore his U&Es.  Our ability to control heart failure is so often hampered by our worrying about the urea rising but I would ignore it.

 

 

 


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Anaemia and CKD III (20)

This diabetic lady has CKD3 with microalbuminuria of 14.8.  She was recently seen in the haematology clinic regarding her chronic anaemia (most recent haemoglobin was 100g/l).  She was in hospital at the end of last year when she was transfused and started on oral iron.  At that time endoscopy was normal but she has previously had angiodysplasia.  Haematology felt this is most likely anaemia of chronic disease rather than iron deficiency anaemia, and that it probably relates to her deteriorating renal function.  Her most recent eGFR was 52, creatinine 91 and urea 8.6.  They have suggested that she might be a candidate for EPO injections to boost her blood count.  I wonder if I should be referring her to renal clinic?

What further information would you seek before giving your opinion?

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B12 and folate are normal.  Ferritin 85, Transferrin saturations 17%

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Renal anaemia with a GFR above 30ml/min is extremely unusual indeed.  10% of anaemia in CKD 3 is explained by EPO-deficiency, but the patients involved are in the eGFR of 30-35 bracket, rather than 52 as in this case.  Given the history of previous angiodysplasia this is most likely the explanation for the recurrent anaemia.


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Anaemia and CKD in the frail elderly (19)

This rather frail 85 year old man has recently become anaemic.  His haemoglobin has dropped down to around 9.0 having previously been around the 11 mark.  Haematinics are normal.  His latest renal function shows urea 15.6, creatinine 213, potassium 4.8 and eGFR 26.

His general health is poor.  He lives at home and is slowly mobile with a zimmer but has had falls and is awaiting a residential or nursing home placement.

Can we attribute his anaemia to his CKD and should he be considered for EPO?  Or should we refer him to haematology for further assessment of his anaemia?

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Co-morbidities include: recent significant stroke, diabetes, angina, Parkinson’s disease, atrial fibrillation, hypertension and LVF.

 Currently: ACR 155, PCR 260, Ferritin 60.

12 months ago: Hb 10.5, urea 11.4, creatinine 168, ACR 120, PCR 185

3 years ago: ACR 35

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This gentleman has evidence of progressive CKD – now Stage 4 – almost certainly secondary to diabetic nephropathy given the longstanding albuminuria and proteinuria.  His anaemia has been evident for some time.  His haematinics do indicate that he may be Fe deficient – his ferritin is only 60 (we would normally look for a minimum of 100). His iron saturation has not been done but should be >20%.   I would suggest in the first instance repeat of his iron stores specifically to include iron saturation and ferritin.  If they are below targets then I would suggest oral iron supplementation.

 I don’t think there is a good indication for a renal clinic referral, but he may be a candidate for erythropoietin therapy if he remains anaemic when iron stores are replete.

 

 


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Creatinine rise on losartan (18)

A 60 year old lady on losartan and simvastatin had bloods done 3 months ago which showed urea 5.4, creatinine 70 and eGFR 81.  Repeat bloods this week showed urea 5.0, creatinine 138 and eGFR 35.  I advised her to stop her losartan and rechecked it the following day and it improved to urea 5.4, creatinine 81 and eGFR 68.

I have advised her to stay off her losartan and aim to check her BP next week and will consider felodipine for her hypertension.

Do I need to do anything further to investigate this lady or should I just avoid ARBs and ACEi and treat her hypertension as required with felodipine?

What further information would you seek before giving your opinion?

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She has a history of ischaemic heart disease and peripheral vascular disease.

No urine has yet been sent for protein quantification.

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If this represents a doubling of serum creatinine with no other precipitant then this is suggestive of renal artery stenosis, particularly if she has vascular disease elsewhere.

On the other hand, if she was unwell when the creatinine rose then this may just be the combined effects of dehydration and losartan.

The key issue would be if the urine dipstick is positive for protein.  If she were to have proteinuria then one could argue the need for recommencing losartan again.  If she has proteinuria and creatinine rises again with losartan then it would be reasonable to refer her to the renal clinic.


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Hypertension, renovascular disease and ACEI (17)

This 65 year old lady has a history of resistant hypertension and renal artery stenosis.  She previously had angioplasty to the left renal artery in 1994 and 1997 and had a right renal artery stent inserted in 2002 for an ostial stenosis.  She has been maintained on antihypertensive treatment since, though good control has never been obtained.

 She was kept on lisinopril until she was admitted with a haematemesis 2 years ago.  Her lisinopril was stopped but reintroduced and titrated up to 10mg. Her potassium rose to 5.6 on repeated measurement and lisinopril was stopped.

 Blood pressure control remains poor with levels typically around 170-180 systolic.  Do you think it would be a good idea to give her a small dose of lisinopril again?

What further information would you seek before giving your opinion?

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Her eGFR has slowly declined and is 43 at present and PCR is 117.

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She was well on her previous ACEI & her baseline state hasn’t changed.  It was, and always is, approriate to stop her ACEI when she was critically unwell, but she is now well, hypertensive & proteinuric, so yes – give her the lisinopril back & watch and see what happens to her U&Es.  I would accept up to a 20% increase in creatinine and potassium up to 6.


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Optimising an ACEI (16)

An 83 year old woman attends the GP surgery for a blood pressure review.

Blood pressure has been high for a while (systolic ~160).  She was taking ramipril 1.25mg and diltiazem HCL 360 mg OD.  She had been taking bendrofluazide but this was stopped during a recent hospital admission due to hypokalaemia.   BP a couple of weeks ago is still very high with values of 218/93 and 200/100. Consequently, I initially increased her ramipril 10 days ago to 2.5mg OD.  Her BP this week is 210/78 and repeat U+Es were ok, so I increased the dose again to 5mg.

She is sytemically well other than for a recent altered bowel and mild weight loss for which she has been referred to colorectal.

I was planning to increase ramipril to 10mg as tolerated but I am not sure how quickly I should be increasing the dose.   I am concerned about her high BP and also concerned about increasing the dose too quickly due to her age.  I also wonder if she requires any further investigation in view of her significant proteinuria?

What further information would you seek before giving your opinion?

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Urine  ACR 467 and PCR 259.  No haematuria.  Her eGFR is 50 and stable.

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You’re doing all that I’d do. The proteinuria level is technically above the recommended referral threshold (PCR 100), but at her age I’d be unlikely to go on to do a biopsy unless she was actually nephrotic or had deteriorating function.   In view of the proteinuria, maximising ACEi would be my first step too.   This can be done quickly (days to weeks) provided BP and renal f(x) are monitored.

 If her eGFR drifts down or there is an increase in proteinuria then it would be worth referring her to the renal clinic. That said, you can allow up to around a 20% rise in creatinine around the time of institution of ACE inhibition.


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Incidental finding of a small scarred kidney (15)

A 60 year old lady has recently been found to have a small scarred right kidney.  This was discovered incidentally when having an abdominal ultrasound scan to investigate slightly deranged LFTs.  Her left kidney is normal.

The scan was arranged by the dermatologists who have been seeing her because of intermittent facial swelling since June 2008.  They think she has angioedema and have started her on various antihistamines.  Other PMH includes self-limiting sarcoidosis, fibromyalgia, hypothyroidism and hypercholesterolaemia, which is well controlled on a statin.

Should I be arranging any more tests on her and if so, which?

What further information would you seek before giving your opinion?

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Results of investigations are as follows;

Blood – Urea 4.2 / Creatinine 82 / eGFR >60,

Urinalysis normal – ACR 2.9.

Last BP 108/60.  No history of hypertension.

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The answer is simple – do nothing.  This is almost undoubtedly the end-stage of a chronic process, quite possibly childhood reflux.  Her left kidney has compensated for the loss of the right without any obvious harm in that her creatinine is normal, she’s not hypertensive and she has no proteinuria.

As she’s managing on only one kidney you need to be vigilant in case of later development of problems such as hypertension, diabetes etc, but at this stage I’d reassure her that she’s done very well, has a relatively common complaint and should not be alarmed.


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