Impact of long term darbepoetin alfa therapy on hyperleptinemic uremic patients on maintenance hemodialysis

In patients with chronic renal failure, the administration of darbepoetin alfa for correction of anaemia, is possibly associated with amelioration of fatigue, exercise tolerance, sense of well being, and better quality of life. As hyperleptinemia is a widely spread phenomenon in uremics, affecting their appetite and nutritional status, we studied the influence of darbepoetin alfa therapy on hyperleptinemia in those patients

Methods: We studied the influence of 12 month therapy of darbepoetin alfa, on 14 patients, [6 males and 8 females], G.I., with mean age [y] of 52.36 +/- 8.6, mean BMI[Kg/mz] [body mass index] of 22.37 1.5, and mean duration [m.] of hemodialysis [H.DX.] of 9.79 +/- 3.7, in comparison with 16 patients, G.II.[treated only by clinical observation]: [8 males and 8 females] with mean age [y.] of 49.19 +/- 7.7, and mean BMI[Kg/rm] of 22.25 +/- 1.0, and mean durationfm.] of H.DX. of9.63 +/- 4.5, as well as, 30 healthy controls [G.III.] matched for age[y.] [mean of: 46.47 +/- 7.8] and sex, and mean BMI of 22.47 +/- 1.4

Results: Baseline leptinemia was significantly higher in H.DX. patients [G.l.and II.] as compared with controls. Monitoring of leptin level after 6 and 12 m. in those patients, a statistically significant decline in leptin levels was observed in darbepoetin alfa-treated patients [G.I.], as compared with patients of G.II., treated only by clinical observation

Conclusion: We found that darbepoetin alfa therapy in hemodialysis patients with chronic renal failure is followed by a significant decline of leptinemia, which may be of clinical relevance in this group of uremic population

HD is beneficial for enzymatic conversion of some amino-acids in the elderly

Many different causes of abnormal amino acid profile in uremic patients including: inadequate nutritional intake, uremic disturbances in amino acid metabolism, loss or fibrosis of renal tissues, metabolic acidosis and hormonal derangement. Some of these factors; such as metabolic acidosis are particularly corrected with dialytic therapy; but others such as decreased intake or hormonal disturbances may persist or worsen after initiation of dialysis. This study was done to investigate the plasma amino acids profile in uremic elderly patients. The present study was carried out on three matched groups: [G1] on HD, [G2] CRF and a control. A significant uniform decrease of Threonine, Valine and Leucine in both HD and CRF. However, a peculiar situation of significant increase in phenylalanine in HD in comparison to CRF and to control. This is similar to the significant increase of Arginine in HD group in comparison to the others. In contrast, phenylalanine was significantly decreased in CRF in comparison to both HD group and the control. The latter was similar to the decrease of Leucine in CRF in comparison to the other two groups. Hence, Phenylalanine was the only AA that was found to be significantly increased in HD and significantly decreased in CRF in comparison to control. Moreover, only Phenylalanine and Arginine were significantly increased in HD group in contrast to the rest of the essential amino-acids, which showed either decrease or no change. Tyrosine and lysine were significantly lower in pre -dialysis CRF group in comparison to patients on HD and the control. This may imply that HD can correct the deficiency of tyrosine and lysine in uremic patients probably due to less inhibition of phenylalanine hydrorxylase. Inter-conversion of phenylalanine to tyrosine was reported to be impaired in CRF; whereas tyrosine metabolism per se does not seem to be grossly affected by uremia. However; Serine was significantly lower in both groups of uremic patients in the current study compared with the control group, with no significant difference in-between pre -dialysis patients and patients on HD. In conclusion, our study showed that HD may be beneficial in restoring the enzymatic turnover of certain amino-acids including: Phenylalanine hydroxylase to normalize tyrosine plasma level, Arginine synthetase to convert citrulline to Arginine. On the other hand, HD may be injurious to the production of other amino-acids like serine due to complete lost of the renal tissue that is responsible of its production from glycine

Thyroid failure in advanced chronic kidney disease: role of erythropoietin therapy

The recently described term [nonthyroidal illness syndrome] involve many organs including I he kidney, affection of which is usually associated with thyroid gland hypofunction. We studied the magnitude of thyroids hypofunction in patients with advanced chronic kidney disease [GFK <30 ml/min] before [N-60] and alter [N 60] dialysis compared to normal subjects. The effect of the commonly used erythropoietin for treatment of anemia in dialysis patients on thyroidal illness, was also studied [N 30], compared with non-Epo treated patients [N=30].We found that 21.66% of predialysis patients were hypothyroid, 69.23% of them were subclinical. Thyroidal illness [hypofunction] appeared to be increasing as severe as kidney function was deteriorating [GFR in euthyroid patients-18.44 +/- 7.18 compared in hypothyroid patients= 12.5 +/- 2.38. P<0.05]. 1n hemodialysis group, all cases [3.33% and 6.67% in subgroups ll a and b. resp.] had clinical hypothyroid ism. No relation was found between thyroid affection and the duration of hemodialysis [P>0.05]. Female gender, elderly patients and patients with type I. D.M. seemed to be more likely 10 be hypothyroid. Lastly, erythropoictin treated patients had a lesser likelihood to have their thyroid gland failed[2.65 +/- 1.96 and 3.17 +/- 2.56 for mean TSH [p<0.05], and 3,33%and6.67% for prevalence of hypothyroid ism in Epotreated and non-Epo treated groups resp.

Value of adenosine deaminase determination in the diagnosis of tuberculous ascites

Tuberculous peritonitis [MP] is a common problem in the developing world. A number of diagnostic tests have been described, but none proved to be of sufficient sensitivity and specificity. The gold standard remains laparoscopy with direct biopsy, yet it is invasive and not always available. Ascitic fluid adenosine deaminase [ADA] activity has been proposed as a useful diagnostic test. The present study was performed to determine the diagnostic utility of ascitic fluid ADA in the diagnosis of TBP. The study included twenty five patients with ascites, they were divided into 2 groups: Group 1 included 13 patients with TBP, Seven had TB peritonitis and cirrhosis, and six had TB peritonitis in the absence of cirrhosis [isolated TB peritonitis]. Group 2 [control group] included 12 patients with ascites of different etiologies, 7 had liver cirrhosis, 2 had nephrotic syndrome, and 3 had malignant ascites. Adenosine deaminase activity in ascitic fluid was examined in patients with confirmed TB peritonitis and compared with that of patients in the control group. The results showed that abdominal swelling was the most frequent symptom, while ascites was the most frequent sign of TB peritonitis, all TB peritonitis patients had exudative ascites with lymphocytes predominance in 76%. The mean adenosine deaminase activity was significantly higher in the ascetic fluid of the tuberculous peritonitis group [52.62 +/- 16.08 IU/L] than in the non-tuberculous group [16.17 +/- 7.99 IU/L], P < 00001. ADA showed a sensitivity and specificity of 92.3% and 100%, respectively. In conclusion: adenosine deaminase activity determination in ascitic fluid is a useful less invasive screening test in the diagnosis of peritoneal tuberculosis, particularly when more invasive diagnostic methods via peritoneoscopy and laparoscopy are not available

Pyrin / marenostrin mutations [M694V and V726A] in Egyptian patients with familial Mediterranean fever

Diagnosis of familial Mediterranean fever [FMF] has until recently been based on clinical signs alone. Undiagnosed patients with Familial Mediterranean Fever [FMF] are at risk for developing amyloidosis or for being subjected to unnecessary operations. The gene causing IMF, designated MEFV [Pyrin/ marenostrin] was recently identified and found to be expressed in mature neutrophils, suggesting that it functions as an inflammatory regulator. The aim of the present study was to search for pyrin mutations [M694V and V726A] associated with familial Mediterranean fever in Egyptian patients

Patients and Methods: the study included 15 patients with FMF, and ten healthy controls. Mutations in the 25 samples were assessed by amplifying genomic DNA with use of three primers that selectively amplify the normal or altered DNA sequence of the 2 MEFV mutations [M694V and V726A] by polymerase chain reaction

Results: showed that in patients with FMF family history was relevant in 6 [40%] patients. Fever and Abdominal pain were present in all [100%] the cases, chest pain in 5 [33.3%], artharalgia in 2 [13.3 %], and six [40%] patients had past history of appendicectomy. M694V mutant was detected in 11 [73%] patients and V726A in 8 [53%], all healthy controls [100%] were negative for both M694V and V726A mutants of MEFV gene and positive for normal MEFV gene with a sensitivity and specificity of 63% and 100% respectively

Conclusion: MEFV gene mutations [M 694 V and V 726 A] seem common in Egyptian patients with FMF. The ARMS assay is a rapid and accurate method for detecting mutations in familial Mediterranean fever. It may be a useful test in detecting patients with atypical clinical presentations, who do not satisfy diagnostic clinical criteria

value of trnsrectal power doppler ultrasonography in cancer prostate

In attempt to assess the usefulness of transrectal power Doppler ultra-sonography [PDU] for improving the diagnoses of cancer prostate in-patients with abnormally elevated PSA, forty male patients with a mean age 65 years were assessed using a digital rectal examination [DRE], transrectal ultrasonography [TRUS] and [PDU]. All cases of prostatitis were excluded. The vascularity on PDU was graded on a scale of 0-3 where grade 0 negative and grade 1-3 was considered positive Transrectal needle prostatic biopsies were obtained from hypoechoic lesions or hyspervascular lesions under TRUS and PDU and systematic biopsy was taken in all cases. The results of PDU, DEE and TRUS were evaluated according to histopathological examination of needle biopsy. Prostatic biopsy confirmed prostate cancer in 11 patients out of 40 patients [27.5%], PDU was positive in 16 patients, of whom 10 had prostate cancer [62.5%], all those but one having prostate cancer were positive on PDU. Thus PDU had a higher sensitivity of 90.9% [10/11], than DRE [54.5%] and TRUS 72.7% and PDU had a higher negative predictive value in 95.8%, while 85% with TRUS and 80.7% for DRE. So, PDU increases the sensitivity and negative predictive value of TRUS in detection of cancer prostate if is it used as a routine investigation with conventional TRUS. This does not need any added manipulations. PDU is more useful for detecting prostate cancer in-patients with abnormally high serum PSA levels and if PDU is negative, needle biopsy may be avoided especially if PSA is not conclusively high