Intradialytic parenteral nutrition for patients on hemodialysis: when, how and to whom?

Hemodialysis is associated with high morbidity and mortality rates as well as low quality of life. Altered nutritional status and protein-energy wasting are important indicators of these risks. Maintaining optimal nutritional status in patients with hemodialysis is a critical but sometimes overlooked aspect of care. Nutritional support strategies usually begin with dietary counseling and oral nutritional supplements. Patients may not comply with this advice or oral nutritional supplements, however , or compliance may be affected by other complications of progressive chronic kidney disease. Intradialytic parenteral nutrition (IDPN) may be a possibility in these cases, but lack of knowledge on practical aspects of IDPN delivery are seldom discussed and may represent a barrier. In this review, we, as a consensus panel of clinicians experienced with IDPN, survey existing literature and summarize our views on when to use IDPN, which patients may be best suited for IDPN, and how to effectively deliver and monitor this strategy for nutritional support.

[Treatment of idiopathic membranous nephropathy. Is the anti-CD20 antibody rituximab a reasonable option?]. / Behandlung der idiopathischen membranösen Glomerulonephritis. Ist der Anti-CD20-Antikörper Rituximab eine sinnvolle Therapieoption?

BACKGROUND: Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure. CASE REPORT: A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and <150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (<150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI). CONCLUSION: Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.

Increased binding of beta-2-microglobulin to blood cells in dialysis patients treated with high-flux dialyzers compared with low-flux membranes contributed to reduced beta-2-microglobulin concentrations. Results of a cross-over study.

BACKGROUND: Patients on long-term dialysis eventually develop amyloid deposits with beta2-microglobulin as a predominant component. Although several studies have suggested that high-flux membranes reduce beta2-microglobulin in plasma compared with low-flux dialyzers, the mechanisms underlying this observation are still discussed. METHODS: We revisited this important subject and measured beta2-microglobulin in the plasma of healthy individuals (n = 8), and patients undergoing hemodialysis (n = 20) who for assigned periods of time were either treated with a low-flux membrane (cuprophan) or high-flux (polyamide) dialyzer with an ELISA. The number of blood cells was determined by FACS. Beta2-microglobulin was also measured on the surface of granulocytes, lymphocytes, and monocytes before, directly after, and 4 h after hemodialysis. Expression of beta2-microglobulin, c-fos, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 mRNA was determined in whole blood samples with quantitative RT-PCR using an internal standard in parallel. In the second part of the study, patients were assigned in a two-group cross-over design either to low- or high-flux dialyzers (n = 9 in each group), and dialyzer membranes were changed every 4 weeks for two consecutive periods. Serum beta2-microglobulin concentrations were measured at the end of each period. RESULTS: Healthy controls had a low plasma beta2-microglobulin level of 1.2 +/- 0.3 mg/l. Before hemodialysis, patients on low-flux dialyzers had a plasma beta2-microglobulin level of 42.0 +/- 14.0 mg/l, patients treated with high-flux dialyzers 21.5 +/- 10.8 mg/l (p < 0.05 vs. low-flux dialyzers). In contrast, there was no significant difference in plasma concentrations of active transforming growth factor-beta1 with the two different membrane types. The difference in serum beta2-microglobulin between low- and high-flux membranes was more prominent directly after hemodialysis as well as 4 h after hemodialysis compared with the values directly before the start of treatment. At all studied time-points, leukocytes and platelets were significantly higher in patients on low-flux membranes. Healthy control persons exhibited a significantly higher amount of beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes compared with dialysis patients. Interestingly, beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes was significantly increased in patients treated with high-flux membranes compared with low-flux filters. Quantitative RT-PCR revealed no significant difference in beta2-microglobulin expression in whole blood before hemodialysis, directly after hemodialysis, and 4 h after hemodialysis. However, TNF-alpha and c-fos transcripts were significantly higher in whole blood obtained from patients treated with low-flux membranes compared to high-flux dialyzers. The two-group cross-over study over three periods of 4 weeks revealed that switching from low-flux to high-flux dialyzers significantly reduced serum beta2-microglobulin levels. CONCLUSION: Patients treated with a polyamide high-flux membrane had lower beta2-microglobulin concentrations compared with those patients on low-flux dialyzers. This difference might not be mediated by an increase in beta2-microglobulin mRNA, but may be caused by less beta2-microglobulin released from the blood cells in patients treated with high-flux dialyzers, in addition to a better beta2-microglobulin clearance.

[Pregnancy-associated thrombotic microangiopathy--a diagnostic and therapeutic challenge]. / Schwangerschaftsassoziierte thrombotische Mikroangiopathie--eine diagnostische und therapeutische Herausforderung.

BACKGROUND: Thrombotic microangiopathies are diseases rarely associated with pregnancy. The pathogenesis might be related to severe preeclampsia and HELLP syndrome. CASE REPORT: In May 2000, we saw a 26-year-old primigravida in the 39th gestational week with worsening anemia, thrombocytopenia, and increasing liver enzymes. The diagnosis of HELLP syndrome was made and delivery initiated. Postpartum liver function stabilized, but anemia, thrombocytopenia, and preexisting hypertension worsened. Additionally, renal function deteriorated, and she had to be dialyzed 12 days after delivery. Renal biopsies were performed on day 12, 34, and 60 after delivery. The material showed a thrombotic microangiopathy, initially in an active stage. Later, fibrosis of the preglomerular arterioles and the glomeruli as well as progressive tubulointerstitial damage could be shown. Plasmapheresis was started; substitution was performed with fresh frozen plasma (FFP). Simultaneously, the patient was treated with corticosteroids. After 24 days, we began with cyclophosphamide pulses. Overall, 28 plasmapheresis sessions and three cyclophosphamide pulses were given. In spite of this aggressive regimen, renal function did not recompensate, and renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD) was initiated. CONCLUSION: This course shows that mortality could be decreased using plasmapheresis therapy, but further research is needed to introduce more specific, kidney-protective regimens.