Background and objectivesThe 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.MethodsIn 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.ResultsThe 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).ConclusionMK 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.

Pregnancy-associated atypical haemolytic uraemic syndrome (P-aHUS) is a rare, potentially lethal condition that can complicate pregnancy in up to 1 in 25 000 cases. Without prompt diagnosis and initiation of appropriate treatment, this condition can lead to disastrous consequences for both mother and child. Given the broad spectrum of conditions that can present similarly in the peripartum period, it is often difficult to establish the correct diagnosis in a timely manner. Recently, the terminal complement cascade inhibitor eculizumab has been used with considerable success in non-pregnancy HUS; however, its use in P-aHUS is limited to isolated case reports. Here, we present a case of fulminant P-aHUS in the postpartum period that was successfully treated with eculizumab resulting in significant recovery of renal function.

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.

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SummaryThe following case describes an ovarian tumour presenting in a highly unusual manner-in the form of a recurrent femoral hernia. Recurrent femoral herniae are unusual and should prompt awareness of underlying pathology causing increased intra-abdominal pressure. BACKGROUND