NP29 Nephrology

Systemic Disease with Renal Manifestation

Essential Med Notes 2015

DIABETIC RENAL COMPLICATIONS

(Urine Protein)
Normal

GFR

1. Progressive Glomerulosclerosis
classic diabetic glomerular lesion: Kimmelstiel-Wilson nodular glomerulosclerosis (15-20%)
more common lesion is diffuse glomerulosclerosis with a uniform increase in mesangial matrix
Table 11. Stages of Diabetic Progressive Glomerulosclerosis
Stage 1

Stage 2

Stage 3

Stage 4

h GFR (120-150%)
compensatory
hyperfiltration
slightly increased
mesangial matrix

Detectable microalbuminuria
(0-300 mg/24 h)
Albumin-Cr ratio
(ACR) 2.020 mg/mEq in
men (18-180 mg/d),
ACR 2.8-28 mg/mEq in
women (25-250 mg/d)
h mesangial matrix

Macroalbuminuria
(>300 mg/24 h)
ACR in men >20 mg/mEq,
(>180 mg/d)
ACR in women >28 mg/mEq
(>250 mg/d)
Proteinuria (+ve urine dipstick)
Normal GFR
hhh mesangial matrix

h proteinuria
(>500 mg/24 h)
i GFR
<20% glomerular filtration
surface area present
Sclerosed glomeruli

2. Accelerated Atherosclerosis
common finding
decreased GFR
may increase angiotensin II production resulting in increased BP
increased risk of ATN secondary to contrast media
3. Autonomic Neuropathy
affects bladder leading to functional obstruction and urinary retention
residual urine promotes infection
obstructive nephropathy
4. Papillary Necrosis
type 1 DM susceptible to ischemic necrosis of medullary papillae
sloughed papillae may obstruct ureter
can present as renal colic or with obstructive features hydronephrosis
2013 Canadian Diabetes Association Clinical Practice Guidelines on Chronic Kidney
Disease in Diabetes
screen for microalbuminuria with a random urine test for albumin to Cr ratio (ACR) and eGFR
with a serum Cr (e.g. using MDRD equation)
type 1 DM: annually in post-pubertal individuals after 5 yr of diagnosis
type 2 DM: at diagnosis, then annually
If eGFR >60 mL/min or ACR <2.0 mg/mEq: there is no CKD, re-screen in 1 yr
If urine ACR >20.0 mg/mEq: diagnose CKD
If ACR <20.0 mg/mEq but >2.0 mg/mEq: order serum Cr for eGFR in 3 mo and 2 repeats of
random urine ACRs over the next 3 mo; at 3 mo: if eGFR 60 ml/min or if >2/3 ACRs are
>2.0 mg/mEq, diagnose CKD
if CKD diagnosed, ordered urine R+M and dipstick, if negative then diagnose CKD in DM
with CKD in DM: urine ACR and serum Cr (for eGFR) every 6 mo
delay screening if transient cause of albuminuria or low eGFR
evaluate for other causes of proteinuria, rule out non-diabetic renal disease
avoid unnecessary potential nephrotoxins (NSAIDs, aminoglycosides, dye studies)
Priorities in the Management of Patients with DM
1. vascular protection for all patients with DM
ACEI, antiplatelet therapy (as indicated)
BP control, glycemic control, lifestyle modification, lipid control
2. optimization of BP in patients who are hypertensive
treat according to HTN guidelines
3. renal protection for DM patients with nephropathy (even in absence of HTN)
type 1 DM: ACEI
type 2 DM: CrCl >60 mL/min: ACEI or ARB CrCl <60 mL/min: ARB
2nd line agents: nondihydropyridine calcium channel blockers (diltiazem, verapamil)
ACEI and ARB can be safely used together if needed for control of significant proteinuria
(monitor for hyperkalemia and acute rise in Cr)
check serum Cr and K+ levels within 1 wk of initiating ACEI or ARB and at time of acute illness
serum Cr can safely be allowed to rise up to 30% with initiation of ACEI or ARB, usually
stabilizes after 2-4 wk, monitor for significant worsening of renal function or hyperkalemia
if >30% rise in serum Cr or hyperkalemia, discontinue medication and consider 2nd line agent
consider holding ACEI, ARB, and/or diuretic with acute illness and in women before becoming
pregnant
consider referral to nephrologist if ACR >60 mg/mEq, eGFR <30 mL/min, progressive kidney
function loss, unable to achieve BP targets, or unable to stay on ACEI or ARB

Time

Figure 17. GFR and urine protein

over time in DM

Renoprotective Effect of Angiotensin-Receptor

Antagonist Irbesartan in Patients with
Nephropathy Due to Type 2 DM
NEJM 2001;345:851-860
Study: Multicenter, RCT, mean follow-up of 2.6 yr.
Patients: 806 patients (mean age 70 yr) with type
2 DM, HTN, and nephropathy (24 h proteinuria
>900 mg, serum Cr 88-265 mol/L [male], serum
Cr 106-265 mol/L [female]).
Intervention: BP control with irbesartan vs.
amlodipine vs. placebo, with use of adjuncts (not
including ACEIs, ARBs, or CCI) as needed.
Outcomes: Primary composite endpoint included
doubling of serum Cr, ESRD, or death. Secondary
composite endpoint included morbidity and
mortality from CVD causes.
Results: BP control was similar in all three arms.
Irbesartan had a relative risk reduction of 20% vs.
placebo and 23% vs. amlodipine for the primary
end point. The irbesartan group had a 33% risk
reduction vs. placebo and 37% reduction vs.
amlodipine for risk of doubling serum Cr. Serum Cr
increased more slowly in the irbesartan group vs.
placebo or amlodipine. No difference in absolute
mortality or secondary end point.
Conclusion: Irbesartan conferred significant
renoprotective benefits in patients with type 2 DM
and nephropathy, independent of blood pressure
lowering effects.

Renal Outcomes with Telmisartan, Ramipril,

or Both in People at High Vascular Risk
(ONTARGET Study)
Lancet 2008;372:547-553
Study: Prospective, multicenter, double-blind, RCT.
Participants: 25,620 patients with median followup of 56 mo.
Intervention: Patients received either ramipril
(10 mg/d; n=8,576), telmisartan (80 mg/d;
n=8,542), or a combination of both drugs
(n=8,502).
Primary Outcome: Composite of dialysis, doubling
of creatinine level, and death.
Results: The number of outcome events was
similar for telmisartan (n=1,147) and ramipril
(1,150; HR 1.00, 95% CI 0.92-1.09), but was
increased with combination therapy (1,233; HR
1.09, 1.01-1.18, p=0.037). The need for dialysis
or doubling of serum creatinine, was similar with
telmisartan (189) and ramipril (174; HR 1.09, 0.891.34) and more frequent with combination therapy
(212; HR 1.24, 1.01-1.51, p=0.038). Estimated
GFR declined least with ramipril compared with
telmisartan or combination therapy (p<0.001). The
increase in urinary albumin excretion was less with
telmisartan (p=0.004) and combination therapy
(p=0.001) than with ramipril.
Conclusion: Renal outcomes were similar in both
telmisartan and ramipril monotherapy. Combination
therapy reduced proteinuria to a greater extent
than monotherapy, but was associated with poorer
renal outcomes.