Abstract:
Diabetic nephropathy (DN) is the leading cause of
end stage renal disease and despite optimum therapy
including ACEI/ARBs, a sizable proportion of
patients with proteinuria progress to renal failure. It is
likely that high renin level induced by RAS (Renin
Angiotensin System) blockade may contribute to this
and vitamin D is found to have an inhibitory effect
over RAS as it reduces renin synthesis. This study
was conducted to examine the effects of vitamin D
therapy on renal functions of patients with DN.
The aims of the study were to determine the
prevalence and associated factors of DN among adult
diabetics attending medical clinics in Teaching
Hospital, Galle (THG) and to determine the effect of
vitamin D therapy on DN, cardiovascular morbidity
and bone mineral density (BMD). Phase 1: Crosssectional
study involving patients with diabetes
attending medical clinics in the THG. Their serum
creatinine and urinary albumin (UA) levels were
checked. Phase 2: A double-blind, randomized,
placebo controlled study to determine the therapeutic
efficacy of vitamin D. Patients with DN (UA >30
mg/g of creatinine) whose estimated glomerular
filtration rate (eGFR) was more than 30 mL/min were
selected and their plasma renin, Parathyroid hormone
(PTH), serum vitamin D, serum calcium, serum
creatinine, fasting blood sugar (FBS), lipid profile,
ECG and bone mineral density (BMD) were done as
baseline measurements. Subjects were randomized
into two groups and treatment group was given
vitamin D3,50000IU (0.25ml) intramuscularly (IM)
monthly for 6 months. The control group received
same volume of distilled water IM. The
investigations were repeated after 6 months of
therapy. BMD was measured at 12months in a
randomly selected subgroup of patients. The mean
(SD) age was 61 (11) years and 75 % of them were
females. Among them 66% had albuminuria
(microalbuminuria-60.9%; macroalbuminuria-
5.1 %). The risk factors for albuminuria were poor
glycaemic control and duration of the disease.
Prevalence of low eGFR was 42.9% (n=174); and it
was associated with age and smoking. Retinopathy
and neuropathy were associated with albuminuria but
not with low eGFR.
Of 155 patients invited, 85 were randomly assigned to two groups after exclusions and 82 completed the
study. After six months, mean reduction of urinary
albumin to creatinine ratio in the treatment and
control group were 51.8 mg/g (P=0.06) and 22.4
mg/g (P<0.001), respectively (between group
difference P=0.001). Significant increase in the
eGFR was observed in the treatment group while
eGFR remained unchanged in the control group
(P=0.006 for the between-groups difference). Mean
reduction in plasma renin in the treatment group and
control group were 5.85 pg/mL (P < 0.001) and 0.95
pg/mL (not sigficant), respectively. After vitamin D
treatment, total body BMD, total body BMC (bone
mineral content) and BMDs of total spine, femoral
neck and total hip regions increased by 2.0%, 2.2%,
and 1.8%, 2.1% and 2.6% (P<0.05 for all),
respectively in the treatment group. In the same
group after 6 months of stopping treatment, marginal
but a statistically significant reduction of total BMD
and BMC was observed (P=0.009) while all regional
BMDs remained unchanged. In the control group,
none of the BMD/BMC measurements changed
significantly during trial and post-trial period. No
significant effect was observed in cardiovascular risk
scores. In conclusion, vitamin D3 has beneficial
effects on patients with diabetic nephropathy.
This study was performed at the University o f
Ruhuna, Sri Lanka and the results were included in a
thesis with two published papers for a PhD degree
with the University o f Ruhuna, Sri Lanka and
defended the thesis on 19lh o f February 2015.