A 16 year old girl with oedema

A 16 year old girl presents to Queen Elizabeth Hospital, Blantyre with a two-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. Some kind of antimicrobial was prescribed a month ago, but the swelling was present then and has increased since.

On examination she is slim but has marked bilateral pitting pedal oedema and facial puffiness; her abdomen is also distended, with shifting dullness.  She is apyrexial.  General examination is unremarkable.  Her BP is 112/65, 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.  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?
  2. Renal biopsy is not immediately available here.  What management will you recommend?  How will you advise her and her parents?

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With 4+ proteinuria and oedema there can be little doubt that she has nephrotic syndrome.  It is ‘pure’ nephrotic syndrome, meaning heavy proteinuria without any haematuria, which puts it at the extreme left hand end of the spectrum (see Glomerulonephritis) and makes it significantly less likely that it is caused by post-streptococcal glomerulonephritis or other disorder more toward the ‘nephritic’ end of the spectrum.

She should severely restrict salt intake: oedema is caused by salt retention.  Diuretics are often required, usually loop diuretics.

HIV is an important condition in this region.  An HIV test is important both because the condition could be a manifestion of HIV affecting the kidney, and because most active treatments for nephrotic syndrome involve immunosuppressive agents.

Minimal change disease would be the most likely explanation in a Caucasian girl.  However FSGS is more common as a cause of nephrotic syndrome in Africans: one of these two conditions is most likely. SLE is very unusual before menarche.

If she is HIV negative, a trial of prednisolone, 1mg/kg/day for a few weeks would be worthwhile.

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This case is was contributed by Fran Th’ng and Gavin Dreyer

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.

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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.

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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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(To follow!)

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?

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Case contributed by Fran Th’ng and Gavin Dreyer