losartan-potassium and Amyloidosis--Familial

the kidney is the major site of erythropoietin production. Many efforts have been made to identify renal erythropoietin-producing cells. Previous studies showed conflicting results, but the predominant localization reported was the peritubular interstitial and tubular epithelial cells. This study was conducted to identify the erythropoietin-producing cells in renal biopsies from 10 cadaveric donors and 45 patients with familial amyloidosis ATTR V30M, thirteen of them with anemia. Familial amyloidosis Type I (FAP-I) is a genetic disorder caused by a transthyretin (TTR) protein variant presenting a single amino acid substitution of methionine for valine at position 30 of the polypeptide chain (TTR V30M). Anemia in FAP-I is associated with inappropriately low serum erythropoietin levels.. erythropoietin expression was detected by in situ hybridization (ISH) and confirmed by laser capture microdissection followed by PCR. Renal segments were identified by immunohistochemistry.. erythropoietin was mainly expressed by epithelial distal tubular cells and collecting tubules and additionally, in a few biopsies, by glomerular cells. A similar expression pattern was observed in donors and FAP-I patients. No increased mRNA erythropoietin expression was found in anemic patients, all of them presenting only a slight expression in medulla and cortex.. these results suggest the distal nephron as the major site of erythropoietin production, and support the notion that an inappropriate erythropoietin production is the cause of anemia in familial amyloidosis ATTR V30M.

Topics: Adult; Amyloidosis, Familial; Anemia; Biopsy; Cadaver; Case-Control Studies; Erythropoietin; Female; Humans; Immunohistochemistry; In Situ Hybridization; Kidney Diseases; Male; Middle Aged; Mutation; Nephrons; Polymerase Chain Reaction; Portugal; Prealbumin; RNA, Messenger

Familial amyloidosis or familial amyloid polyneuropathy (FAP) TTR V30M is a hereditary disease presented, in most cases, as a sensorimotor and autonomic neuropathy. Normocytic and normochromic anaemia was found in 24.8% of symptomatic FAP patients associated to lower serum erythropoietin (Epo) levels. Erythropoietin has been reported as efficient in anaemia correction in this disease. To evaluate the tolerance and efficacy of this treatment, a retrospective longitudinal study with 24 patients was undertaken. Patients were followed for at least 6 months. Haemoglobin, hematocrit, iron status, serum creatinine and urea and r-HuEPO doses were monitored, at 0, 3 months, 6 months and at the end of the follow-up. Long-term use of r-HuEPO proved to be efficient in the treatment of anaemia in familial amyloidosis TTR V30M and, despite the disease progression, no resistance cases to this treatment were observed. Positive side effects, like improvement on orthostatic hypotension symptoms and well-being sensation, contributing to confirm erythropoietin as a drug of choice to treat anaemia in amyloidosis TTR V30M.

Topics: Adult; Amyloidosis, Familial; Anemia; Blood Pressure; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Male; Middle Aged; Mutation; Prealbumin; Recombinant Proteins; Time Factors; Treatment Outcome

Familial amyloid polyneuropathy type I (FAP-I) is caused by a mutant transthyretin (TTR V30M) produced by liver, and orthotopic liver transplantation (OLT) is a widely accepted treatment for stopping the major production of TTR V30M. Anemia affects 24.8% of symptomatic FAP-I patients with low erythropoietin (Epo) levels, suggesting a blockage of Epo-producing cells by local or circulating factors. To evaluate the putative toxicity effect of the mutant protein on Epo-producing cells and consequent Epo production, clinical and laboratory parameters of 20 FAP patients were collected before and after liver transplantation, analyzed and compared. Following OLT, the prevalence of anemia increased, with a significant decrease in transferrin saturation, but without significant change in ferritin. Serum Epo levels remained low after OLT and the observed to expected (O/E) Epo level ratio decreased even further after OLT (O/E < 0.8 rose to 70%). Despite the decrease in creatinine clearance (95.1 to 66.9 ml/min, p < 0.001), a similar median O/E Epo level was observed, independently of the presence of renal failure, excluding an important impact of renal failure on Epo production. The increase of anemia after OLT and the maintenance of a defective endogenous Epo production after liver transplantation excluded an inhibitory effect of the circulating TTR V30M on the Epo-producing cells.

Topics: Adult; Amyloid Neuropathies, Familial; Amyloidosis, Familial; Anemia; Cross-Sectional Studies; Erythropoietin; Female; Humans; Liver Transplantation; Male; Middle Aged; Prealbumin; Retrospective Studies; Treatment Outcome

Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis.. Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters.. Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group.. This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.

Topics: Adult; Amyloidosis, Familial; Biomarkers; Blood Pressure; Creatinine; Dialysis Solutions; Erythropoietin; Familial Mediterranean Fever; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Research Design; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Turkey; Weight Gain