Case one:

Tim, aged 52 years, presents for a routine health review. He has had diet controlled type 2 diabetes mellitus for the past 5 years, is overweight (BMI 26.7 kg/m²) and had borderline hypertension at his last clinic visit. Tim smokes 5-10 cigarettes per day and imbibes 30 g of alcohol per day. His only medication is allopurinol for previous acute gouty arthritis.

Today Tim"s seated BP is 135/90 mmHg. His serum creatinine concentration is 100mmol/L and his eGFR is reported as >60 mL/min/1.73m². His HbA1c is 8.4%, total cholesterol 6.1 mmol/L, and a timed urine collection reveals a urinary albumin excretion rate of 65 mg/day. Four months ago, his urinary albumin excretion rate was 42 mg/day.

Question 1: Does Tim have CKD?

Question 2: Does an eGFR >60 mL/min/1.73 m² mean that Tim has normal kidney function?

Question 3: What treatments would you recommend for Tim?

Question 4: What should Tim"s target BP be?

Question 5: If you start Tim on an angiotensin receptor antagonist (ARA) or angiotensin converting enzyme inhibitor (ACEI), when would you re-check his serum biochemistry?

Question 6: If you start Tim on an ARA or ACEI, how much elevation of serum potassium or serum creatinine (or fall in eGFR) would you tolerate?

Question 7: Which of the following factors is the strongest predictor of cardiovascular (CV) risk in Tim?

A. Diabetes mellitus    B. Smoking    C. Albuminuria    D. Obesity    E. Hypertension

Question 8: Should Tim be referred to a nephrologist?

Answer 1

Tim has had kidney damage, as evidenced by the presence of microalbuminuria (Table 1), for more than 3 months therefore he meets the diagnostic criteria for CKD (Table 2).

Answer 2

Not necessarily. The abbreviated Modification of Diet in Renal Disease (MDRD) formula used to determine eGFR in automated laboratory reports was specifically developed and validated in CKD populations with GFR levels below 60mL/min/1.73 m² and tends to be less accurate in patients with normal or near normal kidney function. Consequently, most laboratories do not currently report a precise figure for eGFR if the value is greater than 60mL/min/1.73 m², even though a normal GFR is generally greater than 90 mL/min/1.73 m². An eGFR value greater than 60 mL/min/1.73 m² may either be normal or abnormal. Under such circumstances, the presence of CKD must be confirmed by demonstrating evidence of kidney damage (eg. microalbuminuria).

Answer 3

• As Tim has CKD (likely due to diabetic nephropathy), the mainstays of his treatment are:
• lifestyle modification
• antiproteinuric agents (ARAs and/or ACEIs)
• optimal control of his BP
• optimum control of cholesterol (target total cholesterol <5 mmol/L), and
• optimum control of blood sugars (target HbA1c <7%)

.Answer 4

According to current national and international guidelines, patients such as Tim who have diabetes mellitus and/or CKD should aim for a BP target of <130/80 mmHg. In CKD patients with more than 1 g/day proteinuria/albuminuria, this target is reduced to <125/75 mmHg.

Answer 5

Less than 2% of patients commenced on ARAs or ACEIs experience a significant decline in kidney function or an elevation of serum potassium concentration. Of those who experience acute kidney failure following commencement of antiproteinuric therapy, roughly half do so within the first week, and most of the remainder do so in the subsequent 3 weeks. It is therefore prudent to check serum biochemistry approximately 1 week and 1 month after commencing an ARA or ACEI.

Answer 6

Current national and international guidelines recommend that clinicans may tolerate up to a 30% rise in serum creatinine and/or a 30% fall in eGFR within the first month of commencing an ARA or ACEI. An initial rise in serum creatinine concentration, which then stabilises and is <30% above baseline value, is predictive of a renoprotective benefit compared with patients who experience no alteration in kidney function at all. It is therefore important not to stop an ARA or ACEI because of a modest rise in serum creatinine or fall in eGFR. If a patient experiences a progressive rise in serum creatinine concentration or an absolute rise of more than 30% above baseline in the first month of ARA or ACEI therapy, the agent should be stopped and consideration given to investigating for the possibility of bilateral renal artery stenosis (eg. with a renal artery Duplex scan). Early alterations in kidney function induced by ARAs and/or ACEIs are nearly always fully reversible on cessation of the medication (even after many years of being on the medication).

Serum potassium concentrations of <6 mmol/L are generally acceptable. Potassium levels slightly greater than 6 mmol/L may be managed by dietary potassium restriction and diuretics. However, persistent elevations or elevations sufficient to require resonium therapy (agent which binds potassium in the gut; not available on the PBS) warrant cessation of ACEI and ARA therapy. Shared management with a nephrologist is recommended in this situation.

Answer 7

Numerous studies, including INSIGHT and IDNT, have shown that albuminuria (including microalbuminuria) is the strongest known predictor of CV risk in type 1 and type 2 diabetes mellitus, hypertension and the general population.

Answer 8

Although Tim has diabetes mellitus together with CKD (microalbuminuria), his eGFR is >60 mL/min/1.73 m². Therefore he does not meet the current Kidney Check Australia Taskforce (KCAT) guidelines for nephrologist referral (Table 3).