A 36 year old soldier developed a flu-like illness (fever, chills, headache, myalgia) 4 days after returning to Jakarta, Indonesia, from a 1 year posting to Papua New Guinea. He was known to have chronic hepatitis B infection, with chronically mildly abnormal liver function tests, but was not on any treatment for this, and had otherwise been well. 3 days later he developed nausea and vomiting and abdominal pain, and jaundice was noted. After a week of this illness he was admitted to hospital where he was thought to have obstructive jaundice, so on the 10th day of his illness he was transferred to a tertiary centre.
Papua New Guinea. CC-BY; credits at foot of page
From the UK Kidney Association’s international case presentation series. This case contributed by Dr Jonny and colleagues from Jakarta, Indonesia.
On transfer he was initially alert, deeply jaundiced, apyrexial, BP 107/53, but becoming obtunded. Some upper abdominal tenderness was noted. Ultrasound showed normal liver oultline no obstruction, thickened gallbladder wall with sludge. Elastography suggested severe liver fibrosis. Blood test results are shown (click to enlarge). The urea converts to 117 mmol/l, Creat 1160 micromol/l. High enough for uraemic encephalopathy. He was also oliguric. He was anaemic, Hb 7.6 g/dl, wbc 19.9 (neutrophilia), plats 462.
The initial suspicion was that he had an acute exacerbation of chronic HBV hepatitis, possibly with acute cholecystitis, complicated by AKI.
- Do you agree? What other conditions would you want to rule out?
- Suggest up to three investigations to rule in or out your key differentials.
What happened next
There are interesting lists of simultaneous jaundice and renal disease
- infective (e.g. Leptospirosis)
- toxic (many, including paracetamol)
- just secondary to severe hepatic disease – hepatorenal syndrome and (perhaps controversially, is it just an epiphenomenon?) bilirubin cast nephropathy.
The key result here was a blood smear.
A revealing test
A blood smear showed Plasmodium falciparum gametocytes, 63 per 500 erythrocytes, 1008 parasites per microlitre. The patient therefore has severe falciparum malaria, with ‘blackwater fever’ and possibly cerebral manifestations (though this could have been just uraemia). The urine did indeed look very dark, which you can also see in rhabdomyolysis, but you can sometimes see similar in severe ATN. Especially perhaps if a patient is jaundiced.
Outcome and further information
He developed multi-organ failure and despite anti-malarial therapy and CVVH (continuous haemofiltration) he deteriorated, developing secondary sepsis, and unfortunately died of septic shock.
Malaria is endemic in Papua New Guinea, but not in Jakarta. He had not been taking prophylaxis while away. The lack of substantial fever probably hindered recognition, and he was treated too late. Simple things.
A 36 year old seamstress from Port Harcourt, Nigeria, presents at 35 weeks of her 6th pregnancy. 3 pregnancies went to term and she has 2 surviving children. She has had hypertension in previous pregnancies, and preterm labour with Caesarian sections; has had cervical cerclage. In this pregnancy she developed leg and facial swelling in the second trimester. She now complains of headaches and insomnia.
The renal team in Blantyre, Malawi, with their first dialysed patient recovered from obstetric renal failure (2014).
From the UK Kidney Association’s international case presentation series. This case contributed by Drs Fakrogha, Oka-Jaja, Ememchioma, David-West, and Prof Wokoma at the University of Port Harcourt Teaching Hospital.
She is restless and distracted. Legs are very oedematous and she has sacral oedema. Blood pressure is 180/100. Urine shows Protein +++ but serum albumin is normal for pregnancy. LFTs are normal.
- What is the most likely diagnosis? Are there any other important possibilities; what else would you like to check?
- What is the correct immediate management?
What happened next
This so far looks most likely to be typical pre-eclampsia. We may wonder later about the recurrent history. The most immediate measures required are
- Control of blood pressure (labetalol IV, oral nifedipine, methyldopa as available)
- Administration of Magnesium
Obstetric ultrasound to judge fetal condition, and size for dates, is valuable if available and there is time. Administration of steroids to protect fetal lungs is desirable if there is time.
She had an urgent Caesarian section, but 6h later had several generalised tonic-clonic seizures, treated with Diazepam. These settled, but at 24h she begins to show petechial haemorrhages and bruising, with mild anaemia but marked thrombocytopenia (estimated by PCV and blood film). Blood pressure remains high but controlled. Her general condition deteriorates over the next days.
On Day 4 she is noted to be oliguric, and thought to be becoming encephalopathic again. Her Creatinine has risen from 85 to 525. On day 8 creatinine has risen further and now she is jaundiced and LFTs (transaminases, ALP not available) are abnormal and albumin 25. Potassium is 4.5. Ultrasound shows normal liver, gallbladder, and kidneys.
- Has your diagnosis changed?
- Are there any other investigations you would do now?
- How would you manage her?
What the experts thought; outcome
The most likely diagnosis remains (pre-)eclampsia. You may now think she has features of HELLP, and she does, but preeclampsia has an extended spectrum of severity and features. HELLP is one way that severe preeclampsia presents.
Management is essentially conservative. Patients with AKI die of high potassium, fluid overload, infection, and lastly uraemia. So managing electrolytes and fluid balance is critical. Dialysis is an extravagant intervention if patients have to pay for it, it is not always an easy option. And it is not a cure, it merely gives more time for recovery, and flexibility with diet.
There was no immediate indication for dialysis and she was managed with low potassium and low salt, low protein, high calorie diet. However she remained oliguric. Creatinine rose further and she became hyperkalaemic, and encephalopathy was not improving, so she received haemodialysis on three occasions. Her urine output picked up after a further 4 days. She improved and creatinine recovered spontaneously.
Postnatal presentation of new features may make you suspect that she could have atypical HUS, but eclampsia is a much more common explanation. In this case, the presentation was entirely typical for eclampsia, and she has had hypertension and features of preeclampsia in previous pregnancies, with full recovery. Sometimes there are minimal or no features before delivery.
Recurrent preeclampsia: an important cause is underlying kidney disease. We don’t know whether this patient had any evidence of CKD or hypertension between pregnancies, or proteinuria in early pregnancy.
MRI T2/FLAIR on day 17
A 36 year old alcoholic man was admitted to hospital with obtunding, jaundice and cachexia. In addition to deranged LFTs, anaemia and thrombocytopenia, all thought to be related to cirrhosis, he had Creat 194 (eGFR 36), Na 138, K 2.6. He was treated for alcohol withdrawal but was difficult to manage; for a few days he was intubated and ventilated. Lactulose was thought to blame for very profuse diarrhoea, and he developed significant electrolyte disturbance. Serum sodium rose to 158 over 30 hours at one point; then slowly improved with water hydration over several days. Potassium rose to 3.4 then dropped back to 2.4 before slowly returning to normal.
5 days later his conscious level reduced again and he developed spastic quadriplegia. An MRI scan later that day is shown above.
Question: what is the likely caused of this problem? Could anything have been done to prevent it?
What the experts thought ...
This is osmotic demyelination (old name: Central Pontine Myelinolysis) but it is a very unusual example caused by rapid onset of hypernatraemia. Usually it is attributed to too-rapid correction of very low plasma [Na], but presumably the principle is the same. A few principles.
- The hyponatraemia needs to be of some duration (not acute).
- The delayed onset of symptoms, 2-6d after the peak change in sodium, is typical.
- A ‘safe rate’ for correction of chronic hyponatraemia is said to be less than 8 mmol every 24h (up to 10 mmol quickly for severe acute symptoms). (UpToDate)(UoE login required).
- Risk factors for its occurrence include alcohol abuse, liver disease, malnutrition, pre-existing brain disease. It is also much more likely if starting sodium is <120.
What happened? He is said to have made a good neurological recovery over a week or so. This is not always the case.
This case is adapted from Am J Kid Dis 68(5):xv-xvii (2016). The image is courtesy of Dr Lemuel Marquez Narcise, Radiopaedia.org, from the case rID: 44204
A 20 year old man complains of 3 weeks of cough and fever, and 4 days of oedema of his feet. On examination he is breathless. There is marked engorgement of his neck veins, JVP higher than ears, ascites, 2+ oedema of his feet. P130/min irregularly irregular, of waxing and waning volume, apex rate 160. BP 95/80. Liver 4cm. There was dullness and reduced breath sounds at R lung base. His chest radiograph is shown.
ECG showed inverted T waves across anterolateral chest leads.
What is the likely diagnosis. What complication sounds imminent, and what would you do about it. What is the most likely cause?
Show what happened next
He has a pericardial effusion with tamponade. 500 mls of bloody fluid were drained from the pericardium, with immediate improvement in breathlessness and blood pressure. 1000 ml of similar fluid was drained from the right pleural cavity. Microscopy did not show a cause.
The effusion recurred a week later, so a pericardial biopsy was undertaken. Don’t try this at home.
A week later the problem recurred. A biopsy was undertaken.
What might it show?
Show the outcome
The fluid again did not give a diagnosis, but the pericardial biopsy showed giant cell granulomas. A guinea pig was inoculated with the fluid, and 5 weeks later it had developed tuberculous lesions, confirming the diagnosis.
TB is a rare cause in UK practice. Viral causes are probably the most common cause of symptomatic acute pericarditis, followed by autoimmunity. However big effusions causing tamponade are probably most likely after cardiac surgery or myocardial injury (Dressler Syndrome), and in malignancy. Infections are a less common cause.
This case is from Sanghvi et al 1958, Sawai Man Singh Hospital and Medical College Rajasthan (Pericardial biopsy with Vim-Silverman needle, Archives of Internal Medicine 101:1147-10). Pushing a big biopsy needle towards the heart sounds hazardous, and probably fortunately the approach didn’t catch on. Guinea pig inoculation was a quicker, less demanding technique than TB cultures, though these had been developed in the 1930s.
Pericarditis from TB is rarely encountered in developed countries now, but still not rare worldwide. Drug resistance, and co-infection with HIV, are important issues. Surgery may be required in chronic examples, but is not always available in the areas of highest incidence.
Further further info
History of tuberculosis (Wikipedia) and Timeline of tuberculosis (Wikipedia) are both fascinating.
The image shows a modified Vim Silverman needle, the predecessor of the ‘Trucut’ cutting needle developed for liver biopsies, extended in the mid 1950s to renal biopsies (Renal biopsy becomes mainstream, 1954).
A 48 year old man is found to have BP 170/95 and a follow-up blood test shows eGFR 55. The abdomen seems to contain hard masses. On following this up, this investigation is undertaken:
After the quiz, a couple more questions
So that’s the diagnosis. What is the prognosis likely to be? Is there anything you can do to alter it?
Show what the experts thought?
This is advanced PKD with very large kidneys and not much normal kidney tissue in between the cysts. This patient is likely to be heading for dialysis and/or a renal transplant. It is amazing that liver failure is extremely rare in PKD, despite sometimes massive cyst formation – though there can be physical symptoms from all this extra volume in the abdomen.
PKD accounts for close to 10% of end stage renal disease in most countries.
Management of PKD has been mostly symptomatic until recently, but the first drug to slow down the progressive growth of cysts is now licensed: Tolvaptan, an ADH receptor antagonist. CKD issues in PKD are the same as for any other patient with renal impairment.
The image shown is courtesy of Prof Frank Gaillard (Radiopaedia)
[pic from Thyolo] A 14 yearl old schoolgirl is referred from Thyolo District Hospital, Malawi, complaining of facial swelling for 3 weeks, worse in the morning. 3 days later she developed bilateral leg swelling and increasing abdominal distension with some suprapubic colicky pains. She reported concentrated urine but no haematuria. There was no significant past medical history but 1-2 weeks previous to her symptoms she was treated for malaria when she had a fever. Anaemia was noted at that time and she was given Albendazole and ferrous sulphate. A week before admission she was treated for vaginal discharge with Gentamicin 240mg IM one dose, and a course of Doxycycline and Metronidazole. She had also taken some herbal medicines for her symptoms.
She now complains of feeling ill, anorexia, and is vomiting once or twice a day.
Her father works on a tea estate as a labourer. The family can afford 3 meals a day.
On examination she was unwell but not distressed, appeared well nourished. Temperature 36.5C, pulse 96, BP 168/94, respiratory rate 16. She had pale conjunctivae and facial oedema that she said was improved. Pedal oedema had also mostly resolved. There were no skin lesions or rash. Throat was normal and she had no lymphadenopathy. Her JVP was not elevated. Heart sounds were normal. There was evidence of some ascites but again this seemed to be improved.
Urine dipstick showed blood 3+, protein 3+, and was negative for leucocytes and nitrite
Before showing results, what syndrome does she have? What do you think the diagnosis is likely to be?
Case contributed by Emmanuel Mwabutwa
Show test results
- HIV test negative
- Pregnancy test negative
- Hb 5.3 (MCV 70), wbc 4.3, plats 170
- Creatinine was 19.3 mg/dl (1700 micromol/l) 3 days ago, having risen from 15.3 mg/dl (1350 micromol/l) 4 days previously.
- Ultrasound showed kidneys to be normal in size but bright in echo pattern. It confirmed ascites. A cardiac echo showed a 1.6cm pericardial effusion but normal ejection fraction (76%) and appearances. The right atrium and hepatic veins were dilated.
Now write what you think and what you'd do
Show what the experts thought?
She has acute nephritic syndrome – fluid retention, hypertension (BP very high for a 14 year old) and renal impairment with strongly positive dipstick tests for haematuria and proteinuria. These confirm glomerular disease.
The most likely diagnosis is classic post-infectious glomerulonephritis. The normal kidney size and lack of left ventricular hypertrophy support an acute condition, rather than an exacerbation of something chronic.
She also has severe anaemia with microcytosis suggesting iron-deficiency. Anaemia is frequent in the population and can be multifactorial related to malaria, diet, or other factors.
Her renal impairment is severe and life-threatening. We do not have a potassium result. Usually post-infectious glomerulonephritis in children resolves spontaneously, and there are probably many sub-clinical cases. At its most severe, dialysis may be required, but good recovery is still usual. Even severe cases can usually be managed conservatively:
- Diet: Limit salt intake (about zero is right if they are oedematous and hypertensive); limit potassium intake
- Restrict protein intake but provide plenty of calories. Oedema can hide severe wasting
- Loop diuretics relieve fluid retention in all but the most severe cases, and improvement in fluid balance improves blood pressure, though additional measures may be required.
This man was diagnosed with interstitial nephritis secondary to mesalazine (prescribed for ulcerative colitis) in 2009. His eGFR has remained stable since and is curently 42. Last year he was started on lisinopril for hypertension but this was stopped some months later as his BP was too low. The plan then was to reintroduce if BP over 130/80 or if proteinuria worsened. Urinary PCR was 15 mg/mmol.
His PCR has increased a bit to 20; blood pressure on his last two visits 123/83, 124/96. I just wanted to check that we should add in lisinopril 2.5mg in vew of this.
I also note that his cholesterol was recently 6.1, LDL 4.2, chol/HDL ratio 4.2. I wonder if we should be starting a statin also? He has no significant family history of heart disease and is an ex-smoker. Other therapy is azathioprine (only) for ulcerative colitis.
Write what you think and what you'd do
Show the answer?
That level of proteinuria, just outside the normal range, wouldn’t trigger me in his case. Any threshold is going to be arbitrary, but 50 is sometimes uesd. Consistently over 50 maybe. His BP is well within limits. His CV risk is low (see Further Info)
Proteinuria is in general a strong marker for progression of renal disease, with higher levels indicating much higher risk. Mostly we are talking about glomerular leaking of protein. He actually had tubulointerstitial disease rather than glomerular, which is associated iwth lower levels of proteinuria in general, and lower risk of progression if the cause is removed (as it is in him).
If he showed any signs of long term deterioration I’d be stricter but he seems to have experience a small fall in creatinine over the last couple of years.
- CV risk calculator gives him a 10y risk of CV events of 3.6% – this does not include proteinuria however, which would ‘usually’ probably at least double risk, though this is contentious in this patient’s unusual circumstances.
- Interstitial nephritis (Edren Textbook)
- The Edrep Glomerulonephritis page has a link to a 10 min lecture on Interstitial nephritis (requires Flash). The Resources page there has more links
A healthy 4 year old boy is brought to the Dermatology clinic at Queen Elizabeth Central Hospital, Blantyre by his parents. He has been scratching his head, and they have recently noticed that he has developed several small scaly areas with associated hair loss.
What is your diagnosis and how would you treat him?
Write what you think and what you'd do
Show the answer?
The diagnosis is tinea capitis (scalp “ringworm”). This is a cutaneous fungal infection which invades the hair shaft and is often due to Trichophyton tonsurans
(caught from other children) or Microsporum canis
(caught from kittens or puppies). Without treatment it gets better spontaneously at puberty. After puberty it only occurs in patients with underlying immunosuppression.
Treatment of choice is oral griseofulvin 15-20mg/kg/day for 6 weeks. Additional application of a topical antifungal, during the early stages of treatment, may reduce the risk of transmission. Terbinafine is an unlicensed alternative, but may not be as effective for infections with M. canis. The only oral antifungal available in the department is ketoconazole, so he is prescribed this and topical Whitfield’s ointment. His parents then tell you that his elder sister was treated with the same treatment successfully earlier this year.
Other siblings with infection should also be treated and if the family pet’s fur is falling out it must be treated too.
The other differential diagnosis to consider in this case is alopecia areata but the presence of scale distinguishes these diagnoses.
This case contributed by Levie Mwale and Ann Sergeant
A 34 year old man presents to Queen Elizabeth Central Hospital, Blantyre with a 2 day history of frontal headaches and generalized tonic clonic seizures. His guardians report that he has had multiple nodules all over his body since childhood but has previously been well.
He has another prolonged seizure after admission. He is post-ictal on examination with a Glasgow Coma Scale 11/15 (E -4, V-2, M-5). His pupils are of normal size and equally reacting to light. His vital signs on admission are: blood pressure 121/81mmHg, pulse 94/min, temperature 37.0°C, respiratory rate 24/min. The chest and abdominal examination are normal. The rest of the neurological exam does not reveal any focal deficits.
- What is his underlying condition?
- What differential diagnoses are you considering?
- What tests would you want to do?
- What would your initial management be?
Write what you think and what you'd do
Show the answer?
The recent history of headaches raises the possibility that this is more than simple epilepsy, though his underlying condition is associated with epilepsy. This is a region where there is a high prevalence of HIV infection, the possibility of which broadens the differential diagnosis importantly.
His underlying condition is neurofibromatosis type 1. It is associated with epilepsy and with astrocytomas, gliomas, but at presentation it may be causative or just a coincidence.
Tests you should seek:
- Blood glucose
- Full blood count
- Malaria blood film
- Lumbar puncture with examination to include India Ink stain (if available you would test for Cryptococcal antigen)
- HIV test
- Urea and electrolytes
- Brain imaging (but CT /MRI not available here)
- Serology for syphilis
- Epilepsy – simple or caused by neurofibromatosis-associated brain lesions
- Cerebral malaria is more likely in children than adults
- Metabolic – DEFG; Don’t ever forget Glucose. Hypoglycaemia may induce coma and convulsions. Other metabolic disturbances including hyponatraemia
- Meningitis – particularly TB or Cryptococcal meningitis in the presence of HIV infection
- Infective focal brain lesions: Toxoplasmosis, primary CNS lymphoma – usually HIV-related; Cysticercosis, neurosyphilis
- Control continuing convulsions with diazepam IV.
Then in this setting:
- Phenobarbitone 600mg loading dose (infusion or slow push) the 90mg maintenance (IM or orally if patient can tolerate it) OR Phenytoin 900mg loading dose (infusion) then 100mg tds maintenance. Blood monitoring is not available.
- Empirical cover for meningitis until CSF results back: Ceftriaxone 2g bd IV
For options in other centres, see …
This case contributed by Dr Tamara Phiri
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.
- What is the differential diagnosis?
- Renal biopsy is not immediately available here. What management will you recommend? How will you advise her and her parents?
Write what you think and what you'd do
Show the answer?
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.
This case is was contributed by Fran Th’ng and Gavin Dreyer