Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and occurs due to multiple factors such as progressive hyperparathyroidism and hyperphosphatemia.1 The vitamin D endocrine system is essential for calcium homeostasis, bone metabolism and immunomodulation.2 Vitamin D deficiency is linked with increased cardiovascular morbidity in dialysis patients.
Patients on peritoneal dialysis (PD) have lo-wer levels of vitamin D due to dietary inade-quacy, decreased sunlight exposure and loss of vitamin D (1,25(OH)2 vitamin D) in the peri-toneal effluent.3 Low levels in dialysis patients are associated with hyperparathyroidism.4 The K/DOQI guidelines recommend measuring 25 (OH) D levels in stages three and four CKD patients with elevated parathyroid hormone (PTH) levels.5
Subjects and Methods
This cross-sectional study was conducted in the PD unit at the KKUH, supported by the Deanship of Scientific Research in King Saud University, in the summer of 2010. All pa-tients included in the study signed a formal informed consent. All patients in the PD pro-gram were considered for the study, but pa-tients less than 15 years, on PD for less than six months, with active malignancy, hemato-logical disorders, post parathyroidectomy or active bone pathology, were excluded.
Based on these criteria, 27 patients under-going regular PD were included in the study. Patients′ age, race, cause of renal failure, presence of diabetes and drugs, including calcium supplements, phosphate binders, calcimimetics and any vitamin D supplements, were recor-ded. Blood samples were taken for serum vita-min D level (25 OH), blood urea nitrogen (BUN), serum creatinine, serum-corrected cal-cium, serum inorganic phosphorous and serum parathyroid hormone (PTH) levels.
The total Kt/V and total creatinine clearance was derived from urea and creatinine levels in 24-h urine collection, dialysate effluent and serum samples. The total Kt/V and total creatinine clearance were calculated using Adequest software program from Baxter Ltd.
Definition of vitamin D deficiency
The results of serum vitamin D level (25 OH) were interpreted as: Levels above 75 nmol/L (30 ng/mL) were considered as normal, levels between 25 and 75 nmol/L (10-30 ng/mL) were considered as vitamin D insufficiency, and patients with serum levels below 25 nmol/ L (6 ng/mL) were considered severe vitamin D sufficiency.5
We analyzed the data using IBM SPSS for Windows, version 18.0. Descriptive data were expressed as the mean ± standard deviation and percentage. We used Student’s t test to compare the various variables and a P <0.05 was considered significant.
The mean age of the patients was 46 ± 21 years. The M:F ratio was 11:16, the mean body mass index was 32 ± 9.45 and the mean urine volume was 353 ± 365 mL/24 h. Ten patients were anuric. Five patients were on continuous ambulatory PD and 22 were on automated PD. The average time on PD was 27.5 months. The etiology of end-stage renal disease was dia-betes mellitus in 11 (40.7%) patients, glomerulonephritis in nine (33.3%) patients and hypertension in three (11.1%) patients. Three patients were suffering from other causes including Systemic Lupus Erythematosis and for one (3.7%) patient, the primary cause was not known.
The mean serum vitamin D 25 (OH) level was 16.1 ± 8.23 nmol/L. None of our patients had 25 OH levels within the normal range [i.e., above 75 nmol/L (30 ng/mL)]. Sixteen (60%) patients had 25 OH <15 nmol/L (severe defi-ciency) while eight (30%) patients had levels between 15 and 25 nmol/L (vitamin D insuf-ficiency).
The average serum creatinine was 701 ± 347.54 μmol/L, the mean serum urea was 17.8 ± 7.09 mmol/L, the mean total Kt/V was 2.15 ± 1/week and the mean total creatinine clea-rance was 78.74 ± 54.5/week. The serum-cor-rected calcium was 2.2 ± 0.2 mmol/L, the se-rum inorganic phosphorous was 1.47 ± 0.37 mmol/ L and the PTH level was 45 ± 39 pmol/ L. Fifteen patients (53.5%) had hyperpara-thyroidism (serum PTH level above 30 pmol/L as per the KDOQI guidelines).5 Twenty-one patients (77.8%) were using calcitriol and 24 (85.7%) patients were on calcium carbonate. Five patients (18.56%) were using Cinacalcet.
The serum 25(OH) D levels reflect the status of vitamin D storage. The K/DOQI guidelines recommend measuring 25(OH) D levels in stages three and four CKD if PTH is elevated.5 A serum 25(OH) D level >75 nmol/L is recom-mended for the general population and CKD stage three and four patients. Replacement with ergocalciferol is recommended if levels are low. No guidelines are given for thera-peutic approaches toward replacement of 25 (OH)D in stage five and dialysis populations. There is limited research available for the prevalence of 25(OH) D deficiency and re-placement in patients with stage 5 CKD. Pro-duction of 1, 25(OH) D appears to be more dependent on 25(OH) D levels in CKD patients.67 Studies have shown loss of vitamin D in the PD dialysate, leading to severe and persistent deficiency.8 Results of a study on PD and hemodialysis (HD) patients by Martensen,9 Renee et al suggest a higher frequency of 25(OH) D inadequacy/deficiency in PD com-pared with HD patients. The prevalence of inadequate/insufficient vitamin D differed bet-ween dialysis modality [31% and 43% insuf-ficient (<50 nmol/L); 4% and 34% deficient (<25 nmol/L) in HD and PD patients, respec-tively (P = 0.002)].
A study by Taskapan et al8 reported 273 PD patients from 20 centers in Greece and Turkey. The results showed that 92% (251 patients) had vitamin D deficiency, i.e. serum 25 (OH) D3 levels less than 15 ng/mL and 119 (43.6%) had severe vitamin D deficiency, i.e. serum 25 (OH) D3 levels less than 5 ng/mL. A study by Nirav Shah et al10 at the University of Pitts-burgh USA in 2005 showed a high prevalence (100%) of inadequate 25(OH) D levels in PD patients at a single center, similar to the results seen in our study. Replacement with oral ergocalciferol once weekly for four weeks showed an increase in the 25(OH)D levels as well as symptomatic improvement. Furthermore, studies with ergocalciferol, or 25 (OH) D therapies, have shown improved serum calcitriol.11
Despite ample sunshine, the Middle East and Africa register high rates of vitamin D deficiency.12 A study by Sadat-Ali Mir et al13 reported prevalence of vitamin D deficiency among 28-37% of the healthy Saudi population. This is partially explained by limited sun exposure due to climate and cultural prac-tices, and skin color. Another study by Elshafie et al14 showed that vitamin D deficiency is very high among Saudi married couples, espe-cially wives. Female gender is an independent predictor of lower vitamin D level, in addition to sedentary life-style and low milk consump-tion. There is a need to revise the levels set for the diagnosis of vitamin D deficiency or insufficiency in the study region.
Another study by El-Menyar et al15 in 547 patients in Qatar reported a high prevalence of low vitamin D (498 patients (91%) with a low vitamin D level <30 ng/mL) in Qatar and countries similar to Qatar in regard with tra-ditional, cultural and environment characteris-tics. Low vitamin D was also associated with a high prevalence of DM, dyslipidemia and coronary artery disease in males compared with females.
A study from Jordan in healthy non-pregnant females16 showed 60.3% (95% CI: 57.1-63.4%) deficiency (<12 ng/mL) and 95.7% (95% CI: 94.4-96.8%) insufficiency (<20 ng/mL) among women.
PD has been used as renal replacement the-rapy in the Kingdom of Saudi Arabia since the 1980s.1718 However, the status of vitamin D deficiency has not been well studied for this population.
In CKD stage three, vitamin D supplemen-tation can be a valuable treatment for preven-ting secondary hyperparathyroidism (SHPT),11 but is less useful in CKD stage four, probably due to insufficient renal one-alfa hydroxyl-lation. In HD patients, monthly ergocalciferol supplementation was efficient in achieving serum 25(OH) D level >75 nmol/L.19 A meta-analysis of prospective trials20 showed that higher 25(OH)D levels were associated with significantly improved survival in patients with CKD. Vitamin D replacement with active derivates can be associated with adverse events including extra-skeletal calcification.21 In a systematic review by Lu Wang et al,22 the investigators independently selected 17 pros-pective studies and randomized trials published in England that examined vitamin D supplementation, calcium supplementation or both and subsequent cardiovascular events. Vitamin D supplements at moderate to high doses may reduce CVD risk, whereas calcium supple-ments seem to have minimal cardiovascular effects.
All of the PD patients in our center are suf-fering from vitamin D deficiency. This can be due to renal disease, dietary restrictions, de-creased exposure to sunlight and loss of vitamin D through PD as well as a reflection of low vitamin D levels seen in the local non-CKD population. Evidence-based clinical guide-lines are needed for optimal management, including vitamin D2supplements and oral vitamin D receptor agonists.
Conflict of Interest
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