Midkine and chronic kidney disease-associated multisystem organ dysfunctions.

Chronic kidney disease (CKD) is a progressive multisystem condition with yet undefined mechanistic drivers and multiple implicated soluble factors. If identified, these factors could be targeted for therapeutic intervention for a disease that currently lacks specific treatment. There is increasing preclinical evidence that the heparin/endothelial glycocalyx-binding molecule midkine (MK) has a pathological role in multiple CKD-related, organ-specific disease processes, including CKD progression, hypertension, vascular and cardiac disease, bone disease and CKD-related cancers. Concurrent with this are studies documenting increases in circulating and urine MK proportional to glomerular filtration rate (GFR) loss in CKD patients and evidence that administering soluble MK reverses the protective effects of MK deficiency in experimental kidney disease. This review summarizes the growing body of evidence supporting MK's potential role in driving CKD-related multisystem disease, including MK's relationship with the endothelial glycocalyx, the deranged MK levels and glycocalyx profile in CKD patients and a proposed model of MK organ interplay in CKD disease processes and highlights the importance of ongoing research into MK's potential as a therapeutic target.

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.

Data quality of the Australia and New Zealand Dialysis and Transplant Registry: a pilot audit.

AIM: Most clinical registries in Australia, including the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), do not audit submitted data. Inaccurate data can bias registry analysis. This study aimed to audit data submitted to ANZDATA from a single region. METHODS: A retrospective audit of individual haemodialysis patient data recorded by ANZDATA at 31 December 2009 was completed by nephrologists in a blinded fashion. Original data were recorded by nursing staff. Patients received treatment at a public hospital, two affiliated satellite haemodialysis units, and three private haemodialysis units. RESULTS: Fifty-one audits were completed of a total 175 patients (29.1%) undertaking haemodialysis in 2009. Primary renal disease was correct in 86.3% (95%CI: 74.3-93.2), although errors in type of glomerulonephritis were common. Date of first dialysis (± 1-month error margin) was correct for 93.6%. Creatinine at first dialysis (± 10% error margin) was correct in 74.4%. Baseline comorbidity accuracy included: peripheral vascular disease (sensitivity 36.4% (95%CI: 24.6-50.1), specificity 82.8% (95%CI: 70.2-90.7)), ischaemic heart disease (sensitivity 69.2% (95%CI: 55.6-80.2), specificity 88.0% (95%CI: 76.3-94.3)), chronic lung disease (sensitivity 25.0% (95%CI: 15.2-38.3), specificity 93.6% (95%CI: 83.4-97.7)), diabetes (sensitivity 86.4% (95%CI: 74.4-93.2), specificity 96.6% (95%CI: 87.5-99.1)), cerebrovascular disease (sensitivity 75.0% (95%CI: 61.7-84.8), specificity 95.3% (95%CI: 85.8-98.6)), and ever smoked (sensitivity 83.3% (95%CI: 70.3-91.4), specificity 71.4% (95%CI: 57.3-82.3)). Non-melanoma skin cancer was under-reported and inaccurate. CONCLUSION: Data accuracy was favourable compared with other renal registry validation studies. Data accuracy may be improved by education and training of collectors. A larger audit is necessary to validate ANZDATA.