A call from the bone marrow transplant unit

They are concerned about the renal function of a 43yo lady who is day 26 post allogenic stem cell transplant for relapsed Acute Myeloid Leukaemia (conditioning with alemtuzumab, melphalan and fludarabine.  Her pre-transplant renal function was normal (creatinine around 60umol/L, eGFR>60ml/min), but has been on a pattern of fluctuating deterioration since around day 5 post transplant, reaching a level today of 415umol/L, eGFR 10ml/min, Urea 17.9, K+ 4.3, Na 143, HCO3 18).  Initial declines co-incided with episodes of sepsis and i.v Gentamicin use.  The patient has also been on Cyclosporin A microemulsion as prophylaxis against graft-versus-host disease, and has had a series of high serum trough levels (generally >300, target <200).  Cyclosporin has now been discontinued and replaced with Tacrolimus, with an initial trough of 15.1, and a Cyclosporin level which is still high at 220. Her weight is currently down 7kg from initial admission, and fluid balance demonstrates ongoing high (2-3L/day) urine output, with around 2L/day oral intake.

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Platelets have been consistently low (<20).
Blood film 2 days ago showed no evidence of red cell fragmentation.
Renal tract USS showed normal sized unobstructed kidneys.
Urine dipstick +haematuria, no proteinuria.
MSU – growing yeasts (further classification pending).

[/wptabs]

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 The cause for this patient’s renal impairment is not certain, with a number of significant differentials

1)   Volume depletion.  Falling weight & high urine output would be consistent with this.  Impaired concentrating ability leading to a high obligate urine output can be a feature of both aminoglycoside toxicity and acute interstitial nephritis

2)   Urinary sepsis.  This will deliver an additional renal ‘hit’ and it is of note further treatment for a fungal urinary tract infection is needed.

3)   Acute Interstitial Nephritis.  The patient has been exposed to multiple courses of antibiotics over the preceding 4 weeks, which would be the most likely trigger & is also on a proton pump inhibitor.

4)   Aminoglycoside Toxicity.  Gentamicin was administered earlier in the clinical course- it seems unlikely this is the sole cause of the current problems but could then contribute to (1) and would be a sensitizing factor to other insults.

5)   Calcineurin Toxicity.  The patient currently has supra-therapeutic and potentially toxic levels of two calcineurin inhibitors at the same time, which have both haemodynamic and tubulotoxic effects on the kidney.

6)   Thrombotic Microangiopathy.  Chemotherapy, malignancy and CNIs are all associated with the development of a renal TMA.  This is associated with low platelets, although in this patients case the low platelets have persisted since her induction chemotherapy, and the absence of red cell fragments is strongly against this diagnosis (as is the lack of blood+protein in the urine dipstick)

Advice:  Efforts should be made to address all reversible factors in the above differential.  Ensure fluid replete and aim for net positive fluid balance over the coming weekend.  Treat sepsis.  From a renal perspective it would be advantageous to withhold Tacrolimus- but the risks of this precipitating GVHD need discussed with her consultant haemato-oncologist.  Suggest repeating blood film with particular attention to features of TMA and checking LDH (raised in intravascular haemolysis).  Check renal function on a daily basis and liase with the renal team.  If renal function continues to deteriorate patient will require transfer into the renal unit for consideration of renal replacement therapy and diagnostic biopsy (although this would be problematic given the current platelet count).

A 25 year old woman with a rash and raised creatinine

A 25 year old woman is referred with a 6 month history of fatigue, joint pain, pleuritic chest pain and facial rash. Three months ago at another hospital she was found to be unwell with a Creatinine of 500 micromol/l, Hb 8.2 g/dl, and urinalysis showed 3+ protein, 3+ blood. She was treated with some tablets (identity unknown) and a subsequent creatinine was 200 and Hb rose to 12 g/dl. Now she is unwell again.

On examination she has a rash around her nose and on her cheeks. She is febrile, 38.2C, and has mild swelling of her left and right MCPJ. She is slim and does not look Cushingoid. BP 155/87. There is no oedema and examination of chest, cardiovascular system and abdomen are normal. She has a platelet count of 50 and Hb 6.2g/dl, Creatinine 430 micromol/l, and urinalysis continues to show 3+ for both protein and blood.

Three questions:

  1. What is the likely underlying diagnosis?
  2. What other urgent (not too complicated) test results are important?
  3. How would you treat the underlying disease given that a renal  biopsy is not possible?

Thanks to Dr Gavin Dreyer for this case.

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Diagnosis:  Lupus seems the most likely underlying diagnosis.

Tests (1) She had a high level of Malaria falciparum parasitaemia. (2) She was HIV non-reactive.
Neither infection would do well with immunosuppressive therapy for lupus. The level of HIV positivity in the region is high, but in sick patients, in particular medical inpatients, it is much higher (up to 80%).
Ideal initial treatment according to WHO should be Artemisinin combination therapy, but it is not generally affordable so Quinine is still most commonly used. She responded to treatment and her Hb rose.

Treatment beyond this point is difficult, but almost certainly she has aggressive inflammatory disease in view of the creatinine changes, and will need cyclophosphamide. Some might argue for MMF in a young woman, but it is less well tested, and much more expensive.

Other diagnostic possibilities?
Classic HIV nephropathy usually has a more extreme nephrotic phase. Of course many other renal pathologies can occur in HIV infection.

Further info

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 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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Gout Prevention in CKD (12)

Please advise on dose titration of allopurinol and gout management in this 62 year old man with CKD3 and multiple medical problems. He recently developed gout with a urate of 0.86. His CKD is stable, with eGFRs usually between 30-40 (latest eGFR 33).

I have given colchicine but pain is persistent and urate still very high.

Past medical history includes; Cor pulmonale, Type 2 Diabetes, COPD, AF, Morbid obesity (BMI 52).

He can attend clinics – would you recommend a medical or renal referral?


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Current Medications; Metformin, Gliclazide, Digoxin, Lisinopril (5mg), Warfarin, Amiodarone, Furosemide (250mg/day)

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I have always thought that response to colchicine is almost useful as a diagnostic test; if he’s getting pain despite colchicine, is it really gout or is it another condition in conjunction with a high urate?

As for allopurinol, start when inflammation has subsided at 100mg / day. In CKD it is recommended to start low dose and titrate dose till urate <.35. Check urea and urate every few weeks.

If we are sure this is gout, and if colchicine is not settling his pain, he could have a short course of steroids‚ something like 5 days of prednisolone (20mg OD), but that may play up with his diabetes.

Does he need to be seen in clinic? – possibly and almost certainly if this problem becomes more complex. If gout control is difficult, rheumatology might be best first stop. His renal function is not deteriorating.

2 further thoughts;
1. He is close to the point where metformin is contra-indicated, in which case he may need to get into the diabetic clinic for advice on insulin
2. He is on a huge dose of furosemide which will undoubtedly push his urate up. If he has cor-pulmonale, I would expect him to have some peripheral oedema because of his right-ventricular pressures. If he is free of peripheral fluid, and especially if his BP is low or low-normal. I would cut his diuretic back a bit, allow him to gain some fluid in order to see what happens.


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Anaemia in CKD (11)

This fairly fit 83 year old lady with a history of hypertension usually has an eGFR around 40.  She is on lisinopril 10mg and furosemide 40mg (best tolerated combination, bendroflumethiazide did not have any effect on blood pressure) and her BP is well controlled on this combination at around 130/68 at her latest visit.

For several months she has had a haemoglobin of around 106 g/l.  Her haematinics and blood indices are otherwise normal apart from a slightly low haematocrit of 0.32.

Is an eGFR of around 40 low enough to cause renal anaemia?  She is only a little tired, are we best just to monitor things?  Should I be looking for another cause for her anaemia?

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That haemoglobin is a little low for that eGFR, but it may be that you find no other cause. There is a big range of Hb values at any eGFR, including at end stage.

It is unusual to drop below 100g/l until eGFR is substantially less than 30, but she isn’t below 100. This level of renal impairment could be compounding another cause and look for deficiencies of haematinics and check a CRP as an indicator of inflammation.

Interestingly ACEi do worsen renal anaemia slightly. However the effect isn’t huge, if this is the best combination for her, she might prefer to tolerate the slightly lower Hb.  Her current level of Hb is above the level at which guidelines would recommend commencing EPO therapy.


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