Dialysate bicarbonate variation in maintenance hemodiafiltration patients: Impact on serum bicarbonate, intradialytic hypotension and interdialytic weight gain.

INTRODUCTION: The dialysate bicarbonate (DB) influences the acid-base balance in dialysis patients. Very low and high serum bicarbonate (SB) have been related with a higher mortality. Acid-base balance also has been associated with hemodynamic effects in these patients. The trial aim was to compare the effect of DB concentration variation on SB levels in maintenance hemodiafiltration (HDF) patients and the effect on intradialytic hypotension and interdialytic weight gain. METHODS: A prospective study, with 9 months of follow-up, involving 93 patients, divided in two groups: group 1 and group 2 with a DB of 34 mmol/L and 30 mmol/L, respectively, with monitoring of pre and post HDF SB, intradialytic hypotension, and interdialytic weight gain. FINDINGS: Pre dialysis SB was higher in group 1: median concentration of 22.7 mmol/L vs. 21.1 mmol/L (P < 0.001). Post dialysis SB levels were higher in group 1: median concentration of 28.0 mmol/L vs. 25.3 mmol/L (P < 0.001). Post dialysis SB in alkalotic range was only detected in group 1 (51.2% of the patients). No significant differences were detected in intradialytic hypotension rate [28.0 vs. 27.4 episodes per 1000 sessions in group 1 and 2, respectively, (P = 0.906)] or in average interdialytic weight gain [2.9% vs. 3.0% in group 1 and 2, respectively, (P = 0.710)]. DISCUSSION: DB of 30 mmol/L appears to be associated with SB levels closer to physiological levels than 34 mmol/L. The bicarbonate dialysate, in the tested concentrations, did not appear to have a significant impact on intradialytic hypotension and interdialytic weight gain in maintenance HDF patients.

Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome.

BACKGROUND: Alport syndrome (AS), a hereditary type IV collagen nephropathy, is a major cause of end-stage renal disease in young people. About 85% of the cases are X-linked (ATS), due to mutations in the COL4A5 gene. Rarely, families have a contiguous gene deletion comprising at least exon 1 of COL4A5 and the first exons of COL4A6, associated with the development of diffuse leiomyomatosis (ATS-DL). We report three novel deletions identified in families with AS, one of which challenges the current concepts on genotype-phenotype correlations of ATS/ATS-DL. METHODS: In the setting of a multicentric study aiming to describe the genetic epidemiology and molecular pathology of AS in Portugal, three novel COL4A5 deletions were identified in two families with x-linked Alport syndrome (ATS) and in one family with ATS-DL. These mutations were initially detected by PCR and Multiplex Ligation-dependent Probe Amplification, and further mapped by high-resolution X chromosome-specific oligo-array and PCR. RESULTS: In the ATS-DL family, a COL4A5 deletion spanning exons 2 through 51, extending distally beyond COL4A5 but proximally not into COL4A6, segregated with the disease phenotype. A COL4A5 deletion encompassing exons 2 through 29 was identified in one of the ATS families. In the second ATS family, a deletion of exon 13 of COL4A5 through exon 3 of COL4A6 was detected. CONCLUSIONS: These observations suggest that deletion of the 5' exons of COL4A6 and of the common promoter of the COL4A5 and COL4A6 genes is not essential for the development of leiomyomatosis in patients with ATS, and that COL4A5_COL4A6 deletions extending into COL4A6 exon 3 may not result in ATS-DL.

Amanita poisonings resulting in acute, reversible renal failure: new cases, new toxic Amanita mushrooms.

BACKGROUND: Renal failure as a consequence of eating mushrooms has been reported repeatedly after ingestion of webcaps of the Cortinarius orellanus group. But mushrooms of the genus Amanita can also cause renal failure: Amanita smithiana (North America) and Amanita proxima (Mediterranean area). Here, we discuss poisonings caused by other white amanitas. A German and--independently--two Portuguese patients reported the ingestion of completely white mushrooms with ring. Similar to intoxications with A. smithiana or A. proxima, the clinical picture was characterized by nausea and vomiting 10-12 h after ingestion, severe acute renal failure and mild hepatitis. Renal biopsy showed acute interstitial nephritis and tubular necrosis. Two patients were given temporary haemodialysis. All have fully recovered their renal function. Poisonings caused by mushrooms containing the toxin of A. smithiana were suspected. We tested 20 Amanita species for the presence of this toxin. METHODS: Thin layer chromatography was applied to detect A. smithiana nephrotoxin in herbarium specimens using authentic material of A. smithiana as reference. RESULTS: A. smithiana toxin could be detected in Amanita boudieri, Amanita gracilior and in Amanita echinocephala. A. boudieri was collected by the Portuguese patients. A. echinocephala is the only nephrotoxic Amanita growing North of the Alps and is suspected to be the cause of renal failure in the German patient. No A. smithiana toxin was detectable in the nephrotoxic A. proxima. CONCLUSIONS: A. boudieri, A. gracilior and A. echinocephala are nephrotoxic. These intoxications are clinically similar to that of A. smithiana, with acute reversible renal failure and mild hepatitis but are different in their clinical picture from Orellanus syndrome characterized by a delayed onset of severe and often irreversible renal failure.

Haemolytic uraemic syndrome associated with H1N1 influenza.

Haemolytic uraemic syndrome (HUS) is one of the two forms of thrombotic microangiopathies and is characterized by the triad of microangiopathic haemolytic anaemia, thrombocytopaenia, and acute renal failure. It has been associated with bacterial and viral infections as well as non-infective causes. We report a subject who presented with HUS associated with an influenza-like syndrome which was confirmed as an influenza A (H1N1) infection. There are reports of HUS associated with seasonal influenza, but there have been no reported cases of HUS after novel influenza A (H1N1) in the literature so far.

Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center's experience.

BACKGROUND: Sensitization to human leukocyte antigens remains an important barrier to successful renal transplantation. MATERIALS AND METHODS: Herein we describe our center's experience with a plasmapheresis-based desensitization protocol for highly sensitized patients. Twenty-nine patients had a positive T-cell or positive B-cell lymphocytotoxicity crossmatch against their donors. In some cases, baseline crossmatches were of high titer (e.g., 11 had baseline titers > or =1:32). RESULTS: Twenty-eight of 29 patients were rendered T-cell crossmatch negative and B-cell crossmatch negative/low positive and transplanted. None had hyperacute rejection but 11 (39%) had acute antibody mediated rejection. Median follow-up is 22 months: 25 of the 28 (89%) of allografts are still functioning with mean plasma creatinine 1.5 mg/dL. There was one death because of the transplant or immunsuppression, one case of cytomegalovirus disease and no cases of lymphoproliferative disease. CONCLUSION: This series provides further evidence of the high efficacy of plasmapheresis-based desensitization protocols. Even patients with high baseline crossmatch titers can be successfully desensitized and transplanted. Short- and medium-term outcomes are encouraging but longer-term data are needed.

Risk of technique failure and death in fungal peritonitis is determined mainly by duration on peritoneal dialysis: single-center experience of 24 years.

Fungal peritonitis (FP) is an infrequent cause of peritonitis in peritoneal dialysis (PD), but it has high morbidity and mortality. We analyzed the experience with FP in a single PD unit over a 24-year period. We identified 671 episodes of peritonitis that occurred in 496 patients during the study period. Of these episodes, 23 (3.4%) were FP episodes occurring in 21 patients. In the FP episodes, the patients' mean time on PD was 29.2 +/- 27 months. In 5 episodes, the patients had experienced a peritonitis episode within the preceding month, and in 11 episodes, the patients had used antibiotics within the preceding month. The FP diagnosis was made a mean of 3.17 +/- 3 days after the diagnosis of peritonitis, and in 1 patient, the diagnosis was made after death. Candida spp. were isolated in 82.6% of patients. In 91.3%, the peritoneal catheter was removed. After the FP diagnosis, 15 patients dropped out of PD, but in only 8 patients (34.7%) was drop-out related to FP. In 4 patients, drop-out occurred because of peritoneal membrane failure, and 4 patients (17.4%) died. Time on PD was significantly higher in the group of patients that dropped out of PD because of the FP (45.7 +/- 31 months vs. 19 +/- 18 months, p = 0.02). Fungal peritonitis is a rare cause of peritonitis in PD patients, but it is associated with high morbidity and mortality. Longer time on PD is the main factor in technique failure and mortality.