Urine and serum midkine levels in an Australian chronic kidney disease clinic population: an observational study.

BACKGROUND AND OBJECTIVES: The cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication. METHODS: In this observational, single-centre study, demographic data were collected, and serum and urine assayed from 197 patients with CKD and 19 healthy volunteers in an outpatient setting. RESULTS: The median serum and urine MK level in volunteers was 754 pg/mL (IQR: 554-1025) and 239 pg/mL (IQR: 154-568), respectively. Compared with serum MK in stage 1 CKD (660 pg/mL, IQR: 417-893), serum MK increased in stage 3 (1878 pg/mL, IQR: 1188-2756; p<0.001), 4 (2768 pg/mL, IQR: 2065-4735; p<0.001) and 5 (4816 pg/mL, IQ: 37477807; p<0.001). Urine MK levels increased from stage 1 CKD (343 pg/mL, IQR: 147-437) to stage 3 (1007 pg/mL, IQR: 465-2766; p=0.07), 4 (2961 pg/mL, IQR: 1368-5686; p=0.005) and 5 (6722 pg/mL, IQR: 3796-10 060; p=0.001). Fractional MK excretion (FeMK) increased from stage 1 CKD (0.159, IQR: 0.145-0.299) to stage 3 (1.024, IQR: 0.451-1.886, p=0.047), 4 (3.39, IQR: 2.10-5.82, p=0.004) and 5 (11.95, IQR: 5.36-24.41, p<0.001). When adjusted for estimated glomerular filtration rate, neither serum nor urine MK correlated with primary CKD diagnosis or CKD progression (small sample). There was a positive correlation between protein:creatinine ratio and FeMK (p=0.003). Angiotensin blockade (adjusted for proteinuria) was associated with lower urine MK (p=0.018) and FeMK (p=0.025). CONCLUSION: MK levels sequentially rise with CKD stage beyond stage 2, and our data support existing animal evidence for an MK/renin angiotensin-system/proteinuria relationship. To what extent this is related to renal clearance versus pathology, or the consequences of chronically elevated MK levels requires further exploration.

Atypical fractures associated with bisphosphonate use post-renal transplantation.

Bone disease is a major cause of morbidity post renal transplantation. The authors present a case of adynamic bone disease and atypical fractures associated with the use of bisphosphonates following renal transplantation. The uncertain role of parathyroidectomy and bone mineral density scans is also reviewed.

Impact of non-traditional phosphate binders and cinacalcet on haemodialysis patient biochemistry, pill burden and cost.

AIM: The Australian Pharmaceutical Benefits Scheme (PBS) commenced cost subsidization for haemodialysis patients of sevelamer in December 2007, cinacalcet in July 2008 and lanthanum in May 2009. To determine the impact of PBS listing of these medications, we performed a single centre cross-sectional, longitudinal study. METHODS: Dialysis parameters and biochemistry were prospectively collected at 6 monthly intervals for all prevalent haemodialysis patients from October 2007 to April 2010. Medications prescribed to manage chronic kidney disease mineral and bone disorder were recorded. Univariate regression analysis was undertaken for each variable against time. RESULTS: Patient numbers ranged from 87 to 114 in each period. At baseline, mean age was 68.8 ± 14.3 years, 71% male, 15.1 ± 3.5 haemodialysis hours/week and urea reduction ratio 71.9 ± 9.8%. These variables were unchanged over time. The use of sevelamer, cinacalcet and lanthanum increased (P < 0.001). There was a decrease in the use of aluminium- and calcium-based phosphate binders (P < 0.001) but no change in the use of magnesium based phosphate binders (P = 0.09) or calcitriol (P = 0.11). Serum phosphate (P = 0.13) and parathyroid hormone (PTH) (P = 0.87) were unchanged. Mean 'bone pill' burden fell from 60.3/week to 51.9/week (P = 0.02). Mean pill cost increased from Australian dollars (AUD) 12.85/patient per week to AUD 59.85/patient per week (P < 0.001). CONCLUSION: The PBS subsidization of sevelamer, cinacalcet and lanthanum has changed prescribing patterns, although serum phosphate and PTH remain unchanged. These changes have been at an additional cost of AUD 2444/patient per year. Data to address clinical end-points of mortality and hospitalization is needed to determine if the cost of these newer agents is warranted.