Question 6

You have admitted a 35-year-old patient to your ICU, who presented complaining of shortness of breath, mild headache, lower limb swelling, and passing dark urine.

Initial vital signs are - Temperature 36.7ºC, non-invasive BP 200/110mmHg, respiratory rate 28bpm, heart rate 145 bpm, SpO2 92% on 6l/min oxygen via a Hudson mask.

Clinical examination shows peripheral oedema on lower limb examination.

Dipstick of urine reveals 3+ for blood and protein, Serum creatinine is 550 mmol/L (45-90) and Serum Urea is 23 mmol/L (3.0-8.0).

a.    List six differential diagnosis for this presentation.    (20% marks)

b.    Outline your assessment of this patient.    (80% marks)

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College answer

Aim: To assess the candidate’s knowledge of acute intra-renal failure requiring an assessment (defined as History, Examination, and Investigations as per the Glossary of Terms).

Key sources include: 2016.2 Q13.3 explore one of the causes of intra-renal failure. CanMEDS Medical Expert.

Discussion: This patient had a classic nephritic syndrome presentation of renal failure. Some candidates suggested differential diagnoses including conditions that would account for some but not all the details given in the stem. These candidates did not score as highly as candidates who specifically addressed the clinical stem, for example detailing the glomerulonephritis causes as part of their differential.

Some candidates also included management in their answers, rather than confining to assessment. Management descriptions did not attract marks as the question was specific to assessment as outlined in the stem. Candidates are advised to use the glossary of terms to understand what information is required. The use of the glossary of terms will help focus your answer, improve accuracy of response, and reduce time wasted for no marks gained.

Candidates who did well stated what aspects of the history, examination and investigations were important and why. Well supported reasoning addressed the clinical scenario more effectively than listing general examination and investigation items without any justification. Many candidates focussed on toxidromes, seemingly ignoring the presence of severe proteinuria and lower limb swelling.

Discussion

Question 13 from the second paper of 2016 presented the candidates with a patient whose renal function took a dive following some days of IV antibiotics for lower limb cellulitis. "Give the likeliest cause of her oliguria" was the question, and "interstitial nephritis" was the only acceptable answer because raised eosinophils were the main abnormality on the bloods we were presented with. This time, the examiners decided to ask for a whole host of diagnostic possibilities (six, for only 20% of the mark), focusing most of their attention on the approach to assessment. This is much more difficult to answer, as it requires a deeper analysis than just the generation of differentials (which most trainees at this stage are very good at). 

Differentials for this presentation:

  • Malignant hypertension with secondary MAHA
  • Pyelonephritis
  • TTP/HUS
  • Renal consequences of sutoimmune disease (eg. SLE, myositis with rhabdomyolysis)
  • Neoplasm (eg. multiple myeloma)
  • Renal calculi  (eg staghorn) or partially obstructive renal neoplasm

Alternatively, one may try to structure them like this:

  • Intra-renal
    • Malignant hypertension with secondary MAHA
    • Pyelonephritis
    • TTP/HUS
    • Autoimmune disease (eg. SLE, myositis with rhabdomyolysis)
    • Neoplasm (eg. multiple myeloma)
  • Post-renal
    • Renal calculi  (eg staghorn) or partially obstructive renal neoplasm

But there would probably be little merit in this, as there are too few differentials to really benefit from this approach, and there would not be anything to represent the pre-renal causes, leaving that heading conspicuously empty, and causing the exam candidate to waste precious seconds wracking their brain trying to figure out what pre-renal pathology could give rise to a classically nephritic picture.

Otherwise, it is also unclear whether it would have been better to write "autoimmune glomerulonephritis" or to make all six differentials a different kind of glomerulonephritis, because there surely are a vast variety of these. Just a short list from Couser et al (2014) includes the following:

  • Post-streptococcal glomerulonephritis
  • IgA nephropathy 
  • Anti-GBM nephritis
  • ANCA-positive glomerulonephritis
  • Lupus nephritis
  • Membranoproliferative glomerulonephritis
  • Minimal change disease
  • Focal sclerosing glomerulonephritis
  • Membranous nephropathy
  • Dense deposit disease
  • C3 nephropathy

Anyway, these were not really the main point of this SAQ. This was mainly an "outline your assessment" question, which would have benefited from a "history, physical examination, investigations" sort of structure, as would soon seem logical to anybody who starts writing an unstructured stream-of-consciusness response. The main headings could even be expanded to include specific sub-heading for investigations. What follows is not intended as a model answer, but rather a  list of possible dot points, some combination of which the exam candidates might have included in a successful response:

History

  • Renal failure history (i.e. how damaged were the kidneys before all this)
  • Drug history (nephrotoxins, antibiotics, NSAIDs, ACE-Is, etc)
  • Nephrounfriendly past medical history (hypertension, diabetes, etc)
  • Travel history (being eating weird Swedish sausage?)
  • Family history (eg. polycystic kidney disease)
  • Social / occupational history (solvent abuse, or merely work-related exposure?)
  • Recent infections / exposure (eg. strep throat, enteritis, etc)
  • Autoimmune weirdness (myalgias, GI motility issues, joint aches, random rash, haemoptysis)

Examination

  • Volume assessment
    • Oedema, pulmonary or otherwise
  • Renal exam
    • Ballottability, kidney size (polycystic?)
    • Flank tenderness (pyelonephritis?)
    • Renal artery bruits
  • Search for other contributing diseases
    • Cardiovascular exam for heart failure
    • Abdominal exam for liver failure, ascites, splenomegaly (malignancy)
  • Search for systemic features of autoimmune disease
    • Rash (eg. lupus, dermatomyositis)
    • Muscle swelling/tenderness
    • Lymphadenopathy (malignancy)

Biochemistry, etc:

  • Urinalysis:
    • culture the urine, obviously
    • protein analysis (light chains)
  • Examination of the urine for casts and sediment:
    • Muddy brown (coarse granular) casts and tubular epithelial casts are associated with ATN
    • Red blood cell casts indicate glomerular disease
    • Shredded-looking RBC fragments also indicate glomerular disease
    • Intact-looking red cells suggest some source of bleeding inside the urinary tract, eg. calculi trauma, malignancy, or the haemorrhagic cystitis of cyclophosphamide therapy.
    • Eosinophils in the urine, especially when they comprise in excess of 5% of the total urinary WCCs, may suggest acute interstitial nephritis
    • White cells in excess, and white cell casts specifically, suggest pyelonephritis
    • Pigmented casts may suggest myoglobin as the cause of ATN
    • Urinary myoglobin levels can confirm rhabdomyolysis
    • Urinary crystals suggest some sort of crystalline nephropathy (they might be urate, oxalate, sulfonamides, etc)
  • Bloods for differentials
    • Blood film (MAHA)
    • ADAMTS13 (TTP/HUS)
    • EPG/IEPG (multiple myeloma)
    • Eosinophil count (interstitial nephritis)
    • CK level (would be embarrassing to miss rhabdomyolysis)
  • Bloods for immunology
    • Anti-C1q, IgG, ASOT (for streptococcal GN)
    • Anti-GBM, ANCA (Goodpastures)
    • Anti-MPO, PR3 (ANCA-positive GN)
    • Anti-dsDNA, C3, C4, antiphospholipid (lupus)
    • Streptococcal serology

Imaging

  • Ultrasound (renal artery stenosis, rebnal vein thrombosis, parenchyma, and obviously pelvocalyceal diltataion)
  • CT KUB (to rule out renal calculi and hydronephrosis/pyelonephritis)

Biopsy

  • Renal biopsy and immunohistochemistry or electron microscopy could yield a diagnosis of an otherwise "seronegative" autoimmune process, or make the diagnosis of an infiltrative disease such as lymphoma

References

Couser, William G., and Richard J. Johnson. "The etiology of glomerulonephritis: roles of infection and autoimmunity." Kidney international 86.5 (2014): 905-914.

Hashmi, Mydah S., and Jyotsna Pandey. "Nephritic Syndrome." (2020).

Isbel, Nicole M. "Glomerulonephritis: management in general practice." Australian family physician 34.11 (2005).

Sanjay Subramanian, John A. Kellum, and Claudio Ronco "Oliguria" in: Critical Care Nephrology by Ronco, Bellomo and Kellum (2009) pp. 341

Mindell, Joseph A., and Glenn M. Chertow. "A practical approach to acute renal failure." Medical Clinics of North America 81.3 (1997): 731-748.

Sladen, Robert N. "Oliguria in the ICU: systematic approach to diagnosis and treatment." Anesthesiology Clinics of North America 18.4 (2000): 739-752.