Michael S. Balzer

Got Milk? Breastfeeding and Milk Analysis of a Mother on Chronic Hemodialysis

Purpose Women on dialysis rarely become pregnant. However, the overall rate of successful pregnancies is increasing in this patient population and breastfeeding becomes an option for mothers on dialysis. In this study we performed a systematic breast milk composition analysis of a mother on chronic hemodialysis (HD). Methods Specimens of breast milk and blood were collected in regular intervals before and after HD from a 39-year old woman starting on day 10 postpartum. Samples were analyzed for electrolytes, retention solutes, nutrients and other laboratory measurements. Breast milk samples from low-risk mothers matched for postpartum age were used as controls. Results Significantly higher levels of creatinine and urea were found in pre-HD breast milk when compared to post-HD. A similar post-dialytic decrease was only found for uric acid but not for any other investigated parameter. Conversely, sodium and chloride were significantly increased in post-HD samples. Compared to controls creatinine and urea were significantly higher in pre-HD samples while the difference remained only significant for post-HD creatinine. Phosphate was significantly lower in pre- and post-HD breast milk when compared to controls, whereas calcium showed no significant differences. In terms of nutrient components glucose levels showed a strong trend for a decrease, whereas protein, triglycerides and cholesterol did not differ. Similarly, no significant differences were found in iron, potassium and magnesium content. Conclusion To the best of our knowledge this is the first report on a breastfeeding mother on chronic dialysis. Although we found differences in creatinine, urea, sodium, chloride and phosphate, our general analysis showed high similarity of our patient’s breast milk to samples from low-risk control mothers. Significant variations in breast milk composition between pre- and post-HD samples suggest that breastfeeding might be preferably performed after dialysis treatment. In summary, our findings indicate that breastfeeding can be considered a viable option for newborns of mothers on dialysis.

Potential Impact of Dialysate Magnesium on Intradialytic Hypotension

Numerous beneficial effects on cardiovascular health have been described for magnesium (Mg). Intradialytic hypotension (IDH) is a common complication in hemodialysis patients which contributes to cardiovascular mortality. It has been suggested that higher dialysate Mg (DMg) might reduce the risk of IDH.

Protein kinase C beta deficiency increases glucose-mediated peritoneal damage via M1 macrophage polarization and up-regulation of mesothelial protein kinase C alpha

BACKGROUND Peritoneal membrane (PM) damage during peritoneal dialysis (PD) is mediated largely by high glucose (HG)-induced pro-inflammatory and neo-angiogenic processes, resulting in PM fibrosis and ultrafiltration failure. We recently demonstrated a crucial role for protein kinase C (PKC) isoform α in mesothelial cells. METHODS In this study we investigate the role of PKCβ in PM damage in vitro using primary mouse peritoneal macrophages (MPMΦ), human macrophages (HMΦ) and immortalized mouse peritoneal mesothelial cells (MPMCs), as well as in vivo using a chronic PD mouse model. RESULTS We demonstrate that PKCβ is the predominant classical PKC isoform expressed in primary MPMΦ and its expression is up-regulated in vitro under HG conditions. After in vitro lipopolysaccharides stimulation PKCβ-/- MPMΦ demonstrates increased levels of interleukin 6 (IL-6), tumour necrosis factor α, and monocyte chemoattractant protein-1 and drastically decrease IL-10 release compared with wild-type (WT) cells. In vivo, catheter-delivered treatment with HG PD fluid for 5 weeks induces PKCβ up-regulation in omentum of WT mice and results in inflammatory response and PM damage characterized by fibrosis and neo-angiogenesis. In comparison to WT mice, all pathological changes are strongly aggravated in PKCβ-/- animals. Underlying molecular mechanisms involve a pro-inflammatory M1 polarization shift of MPMΦ and up-regulation of PKCα in MPMCs of PKCβ-/- mice. Finally, we demonstrate PKCβ involvement in HG-induced polarization processes in HMΦ. CONCLUSIONS PKCβ as the dominant PKC isoform in MPMΦ is up-regulated by HG PD fluid and exerts anti-inflammatory effects during PD through regulation of MPMΦ M1/M2 polarization and control of the dominant mesothelial PKC isoform α.

Oxaliplatin pharmacokinetics on hemodialysis in a patient with diffuse large B cell lymphoma

Dear Editor, Oxaliplatin is a widely used chemotherapeutic agent in diverse anticancer regimens [1]. As oxaliplatin is eliminated from the body mainly by the kidneys and its clearance strongly correlates with glomerular filtration rate (GFR), patients with renal insufficiency or end stage renal disease (ESRD) are especially prone to accumulation and drugrelated toxicity [2]. However, the role of extra-corporal renal replacement therapy in oxaliplatin clearance is not clear. So far, pharmacokinetic data is limited to single hemodialysis (HD) treatment cycles and their respective effect on plasma total and plasma free platinum levels [3, 4]. However, there is no data available on the absolute clearance of oxaliplatin from the body by HD, and HD dose as a parameter of oxaliplatin clearance has not been studied so far. Furthermore, long-term effects of HD on oxaliplatin elimination and necessary dose adjustments are lacking. We analyzed oxaliplatin clearances in a 61-year-old anuric HD patient who was referred to our tertiary care hospital in April 2014 with cervical, supraclavicular, and retroperitoneal lymphadenopathy. Histology revealed follicular lymphoma grade 3A, stage IIIA. Due to additional cardiovascular comorbidity, the patient received six courses of rituximab and bendamustine, which led to partial remission as best response. Despite rituximab maintenance, clinical relapse with recurrence in the known localisations plus splenic infiltration and histopathological transformation to diffuse large B cell lymphoma occurred in September 2015. Second-line treatment with rituximab, gemcitabine, and oxaliplatin was chosen. Because of ESRD secondary to polycystic kidney disease requiring regular home HD since 2002 and lack of evidence for long-term oxaliplatin clearance, dosage of oxaliplatin was reduced to 50 mg/m (50 % reduction, Fig. 1b). Sample collection comprised spent dialysate, ultrafiltrate, and serum. Results (Fig. 1a) show a Cmax of total predialyzer serum platinum (1093 μg/L) within the therapeutic range (500–5000 μg/L) before start of HD and a rapid exponential decline during 5 h of HD, which is in line with data from the literature [4]. Preand post-dialyzer platinum concentrations converged after 4–5 h of dialysis with ΔAUC (AUCpre−AUCpost) representing platinum removal on HD. Concentrations after the first and before the second HD did not change significantly, indicating that no additional elimination occurred between day 1 and 2 after oxaliplatin application. Although calculated dialyzer clearance of oxaliplatin (CLdial) was relatively low (28.43 mL/ min), daily dialysis over five consecutive days clearly showed a significant reduction of long-term platinum serum concentration (Fig. 1b). Interestingly, total amounts of platinum in ultrafiltrate (153 μg) and spent dialysate (4815 μg) were unexpectedly low, which may be * Michael S. Balzer balzer.michael@mh-hannover.de