The inception and formation of the theory of hyperfiltration through the ages.

With the rising incidence of metabolic syndrome and progressive kidney disease, efforts to halt this progression have become the mainstay of therapies in the era of modern nephrology. The necessity of one versus two kidneys has occupied the minds of leading scientists and philosophers throughout the ages and has laid the foundation for our understanding of progressive kidney disease. This review focuses on the major discoveries of the leading thinkers who with their paradigm shifting ideas and skepticism pushed the boundaries of our knowledge and shaped the theory of hyperfiltration.

The evolving ecology of risk for hospitalized dialysis patients.

Despite an increased focus on patient safety, changes in resident work rules and contemporary hospital culture often combine to create an environment of potential hazard for the hospitalized dialysis patient. Clinical scenarios are presented to illustrate some of these risks, and suggestions are offered for the protection of patients.

Sorbent hemodialysis: clinical experience with new sorbent cartridges and hemodialyzers.

To recycle spent dialysate, a sorbent hemodialyzer uses a purification cartridge, adapted from water reclamation systems originally designed for the aerospace program. Increasing interest in home hemodialysis has driven a renewed examination of sorbent dialyzer technology, resulting in the development of a modern sorbent hemodialyzer and an array of new sorbent cartridges. Initial clinical experience with the Allient Hemodialysis System and the new sorbent cartridges is presented, with an emphasis on achievable clearances and ultrafiltration, as well as information about symptom profile and electrolyte balance.

Tissue plasminogen activator as a hemodialysis catheter locking solution.

Tunneled hemodialysis catheters require a "locking solution" between treatments to prevent catheter thrombosis. Heparin locks can be unsafe in patients with life-threatening bleeding diathesis because of unintentional anticoagulation. This study was designed to define the hematologic consequences of using tissue plasminogen activator (t-PA) as an alternative locking solution after heparin-free hemodialysis (HF-HD). Following HF-HD, t-PA 2 mg was instilled into each lumen of the dialysis catheter in 10 patients. Euglobulin clot lysis time (ECLT), fibrinogen, D-dimer, and fibrin degradation products were measured during the last hour of dialysis, and repeated 15 and 30 minutes after catheter locking. Dialysis catheter performance was reassessed at the time of the next hemodialysis. Fibrinogen, D-dimer, and fibrin degradation products were elevated at all time points, but did not change after t-PA. ECLT decreased significantly from baseline 15 minutes after catheter locking (217+/-64 vs. 132+/-75 min, p=0.016). ECLT values had returned to baseline (202+/-56 minutes) by 30 minutes. No episodes of bleeding or catheter thrombosis occurred, and catheter performance did not deteriorate. A 2 mg t-PA locking solution preserved dialysis catheter performance. ECLT decreased at 15 minutes, but normalized by 30 minutes, and did not enter the range in which bleeding would be likely. No clinical events were seen during this transient increase in systemic fibrinolysis.

Antibody-mediated rejection following renal transplantation.

Antibody-mediated rejection (AMR) accounts for 20-30% of all acute rejection episodes following renal transplantation. AMR is generally less responsive to conventional anti-rejection therapy, resulting in poor allograft survival. Introduction of C4d immunostaining of renal allograft biopsies and the demonstration of donor-specific antibodies in the recipients have increased our ability to diagnose AMR. Therapeutic options are evolving and include plasmapheresis, intravenous immunoglobulin, immunoadsorption and rituximab, together with intensification of immunosuppression with a tacrolimus/mycophenolate mofetil combination. Future studies might further define optimal therapeutic approach in renal transplant recipients presenting with AMR.

Steroid avoidance in renal transplant patients maintained on a cyclosporine-based protocol.

OBJECTIVE: The aim of this study was to analyze the effect of steroid avoidance, as compared with our pre-existing protocol that contained steroids, on renal allograft and patient survival. Secondary outcomes included body weight, diabetes, hyperlipidemia, and infection. MATERIALS AND METHODS: This retrospective chart review of the results of steroid avoidance was performed in 169 patients who had undergone renal transplant between January 2000 and March 2002 and had received an immunosuppression regimen of cyclosporine, mycophenolate mofetil, and prednisone; and 148 patients who had undergone transplant between November 2002 and November 2004 who had received induction immunosuppression with a steroid taper by postoperative day 4 and were maintained on cyclosporine and mycophenolate mofetil. RESULTS: One-year allograft survival rates, rejection-free graft survival rates, and patient survival rates were 88%, 76%, and 97%, respectively, in the steroid-maintenance group compared with 90%, 74%, and 96%, respectively, in the steroid-avoidance group (P = NS). No differences were detected in multiple secondary variables related to the metabolic effects of steroid therapy. CONCLUSIONS: These data suggest that steroid avoidance can be performed safely and effectively in patients on a cyclosporine-based protocol of immunosuppression. Longer follow-ups are suggested to determine the effects of limited steroid exposure on the metabolic profiles of patients.

Superiority of pediatric en bloc renal allografts over living donor kidneys: a long-term functional study.

BACKGROUND: Growing waiting list for kidney transplantation in the United States makes it imperative to expand donor pool to use of pediatric kidneys. Because en bloc pediatric kidneys double nephron numbers, it would be interesting to learn how they fare compared to living donor kidneys long term. METHODS: Retrospective chart review was performed on all 72 pediatric en bloc and 75 live adult donor kidney recipients transplanted between January 1990 and December 2001. Long term graft function was assessed with glomerular filtration rate (GFR) using the abbreviated modification of diet in renal disease (MDRD) formula. RESULTS: Pediatric donor was 16.9 +/- 11.2 months old and weighed 10.7 +/- 3.8 kg. Nine en bloc kidneys thrombosed at a mean of 4.2 days posttransplantation. Proteinuria was detected later posttransplantation in en bloc group (45.6 +/- 33.6 months vs. 23.4 +/- 16.3 months, P = 0.002). Pediatric en bloc recipients had significantly higher GFR up to 8 years posttransplantation. One-year graft survival was significantly better in live donor group (93.3% vs. 81.9%, P = 0.041) but five-year graft survival rates were similar (86.7% vs. 76.3%, P = 0.125). One-year and five-year patient survival rates were similar between en bloc and live donor groups (97.3% vs. 98.6%, P = 0.585 and 94.6% vs. 93.0%, P = 0.688, respectively). CONCLUSION: Early postoperative graft thrombosis remain a challenge with pediatric en bloc renal transplants, but once the allografts survive early postoperative course, they provide better long-term function than living donor kidney transplants. In order to alleviate burden on waiting list, pediatric en bloc kidneys should be transplanted more often when available.

Clinical consequences of heparin-free hemodialysis.

Heparin-free hemodialysis (HF-HD) has been increasingly used in patients at risk for bleeding, especially in the intensive care unit (ICU). Lack of heparin can reduce solute clearances in continuous hemofiltration; the effect on HD is undefined. Failure to recognize an effect of the anticoagulation strategy upon delivered clearance could contribute to the known problem of underdialysis in the ICU. In addition, the consequences of "locking" dialysis catheters with concentrated heparin solutions are also unclear. This study was designed to define the clinically relevant consequences of HF-HD and catheter locking. In part I, we performed 200 HD treatments on inpatients, of which 100 were performed with heparin, and 100 were performed as HF-HD. We calculated prescribed and delivered Kt/V and dialysis efficiency. In part II, a separate group of 14 patients undergoing HF-HD via central venous catheters had measurement of activated partial thromboplastin time (aPTT) during the last hour of dialysis, as well as 15, 60, and 240 min after catheters were locked with 1:5000 heparin. The prescribed Kt/V was 1.74+/-0.31 for standard HD with heparin vs. 1.66+/-0.36 for HF-HD (p=ns). The delivered Kt/V was 1.42+/-0.32 vs. 1.36+/-0.38 (p=ns). Efficiency was 0.82 vs. 0.84 (p=ns). Baseline aPTT was 28+/-5 s, and increased to 126+/-54 s, 15 min after locking (p<0.0001) and to 71+/-50 s, 60 min after locking (p=0.005). By 240 min, the mean aPTT had fallen to 33+/-9 s (p=0.03), although individual values were still as high as 50 s. The HF technique does not compromise delivery of dialysis to inpatients. Increased treatment time is not necessary. Locking catheters with heparin after HF-HD resulted in prolonged unintentional anticoagulation.

Hemodialysis catheter-associated endocarditis: clinical features, risks, and costs.

Endocarditis associated with vascular access catheters for hemodialysis (HD) is a catastrophic but not widely appreciated phenomenon. Its current incidence, clinical outcome, and associated costs are not easily ascertained. Increasing use of tunneled catheters for HD access may result in a larger pool of patients at risk for endocarditis. We present two representative cases, review recent trends, and assess the current potential for additional cases.