RESUMEN

A reduction of renal kallikrein has been found in non-insulin-treated diabetic individuals, suggesting that an impaired renal kallikrein-kinin system (KKS) contributes to the development of diabetic nephropathy. We analyzed relevant components of the renal KKS in non-insulin-treated streptozotocin (STZ)-induced diabetic rats. Twelve weeks after a single injection of STZ, rats were normotensive and displayed hyperglycemia, polyuria, proteinuria, and reduced glomerular filtration rate. Blood bradykinin (BK) levels and prekallikrein activity were significantly increased compared with controls. Renal kallikrein activity was reduced by 70%, whereas urinary BK levels were increased up to threefold. Renal kininases were decreased as indicated by a 3-fold reduction in renal angiotensin-converting enzyme activity and a 1.8-fold reduction in renal expression of neutral endopeptidase 24.11. Renal cortical expression of kininogen and B2 receptors was enhanced to 1.4 and 1. 8-fold, respectively. Our data suggest that increased urinary BK levels found in severely hyperglycemic STZ-diabetic rats are related to increased filtration of components of the plasma KKS and/or renal kininogen synthesis in combination with decreased renal kinin-degrading activity. Thus, despite reduced renal kallikrein synthesis, renal KKS is activated in the advanced stage of diabetic nephropathy.

Asunto(s)

RESUMEN

UNLABELLED: We report on two siblings suffering from a new congenital tubulopathy. Following normal pregnancies not complicated by polyhydramnios, severe renal losses of potassium, chloride, sodium and magnesium occurred in the first weeks after birth. Calcium metabolism was not affected. The distal tubular chloride reabsorption was considerably decreased in the two siblings (0.25 and 0.28, respectively). Secondary hyperaldosteronism, activation of the kallikrein-kinin system and elevated urinary prostaglandin excretion were observed. The effects of indomethacin, spironolactone and captopril on symptoms, electrolyte wasting, activation of renin-angiotensin-aldosterone and kallikrein-kinin system and prostaglandin synthesis were studied. In spite of persisting elevation of prostaglandin synthesis, captopril decreased electrolyte wasting, polyuria and hyperaldosteronism most effectively. CONCLUSION: We delineate an apparently new disorder characterized by a postnatal onset, an extremely decreased chloride reabsorption with extensive hyperchloriduria and hypermagnesiuria in the presence of normal calcium metabolism. The disorder can be distinguished from other tubulopathies with hypokalaemic alkalosis.

Asunto(s)

RESUMEN

The kallikrein-kinin system (KKS) is involved in the regulation of blood pressure and in the sodium and water excretion. In humans, the KKS is divided functionally into a plasma KKS (pKKS) generating the biologically active peptide bradykinin and into the tissue (glandular) KKS (tKKS) generating the active peptide kallidin. The objective of this study was to examine the effect of a low-NaCl diet on the concentration of both pKKS and tKKS in plasma and urine in 10 healthy volunteers. After a 4-day low-NaCl diet, the urinary sodium and chloride excretions had decreased from 234 to 21.2 mmol/24 h and from 198 to 14.6 mmol/24 h, respectively. The plasma levels of ANG I, aldosterone, and angiotensin converting enzyme (ACE) significantly increased from 50.4 to 82.8 pg/ml, from 129 to 315 pg/ml, and from 46.4 to 59.8 U/ml, respectively, demonstrating the physiological adjustment to the low-salt diet. In plasma, the levels of bradykinin and plasma kallikrein had significantly decreased from 13.7 to 7.57 pg/ml and 14.4 to 7.13 U/ml, respectively. However, the levels of high-molecular-weight kininogen (HMW kininogen) remain unchanged (101 vs. 112 microg/ml, not significant). Contrary to plasma kallikrein, the plasma levels of tissue kallikrein increased (0.345 vs. 0.500 U/ml; P < 0.01). The plasma kallidin levels, however, did not change (64.7 vs. 68.6 pg/ml, not significant). This can be explained by a simultaneous decrease in the plasma low-molecular-weight kininogen (LMW kininogen) levels (89.9 vs. 44.4 microg/ml; P < 0.05). As in plasma, we find increased urinary concentrations of renal (tissue) kallikrein (23.3 to 42.8 U/24 h; P < 0.05) that contrast with, and are presumably counterbalanced by, urinary LMW kininogen levels (77.0 vs. 51.8 microg/24 h; P < 0.05). Consequently, in urine low-NaCl diet caused no significant change in either bradykinin or kallidin (9.2 vs. 10.8 microg/24 h, and 10.9 vs. 10.3 microg/24 h). It is concluded that the stimulation of the renin-angiotensin system on a low-NaCl diet is associated with a decrease in pKKS (bradykinin and plasma kallikrein) but not in tissue and renal KKS. Although tissue kallikrein is increased, there is no change in kallidin, as LMW kininogen in plasma and urine is decreased. These data suggest a difference in the regulation of pKKS and tKKS by low-salt diet.

Asunto(s)

Asunto(s)

RESUMEN

Total hip replacement is considered one of the most effective treatments in modern medicine. Thus in recent years loosening of total hip prosthesis in elderly patients has become increasingly frequent. An analysis and follow-up study of 63 operations with replacement of hip prostheses evaluating the intra- and postoperative complications shows good results in 50 to 85% concerning pain, function and mobility after a 3-year period. The extended operation matches with a significant win of life quality.

Asunto(s)

RESUMEN

The renal kallikrein-kinin system (KKS) was studied in pair-fed streptozotocin (STZ)-induced diabetic rats and compared with age-matched controls. Twelve weeks after STZ injection, rats were normotensive, showed hyperglycemia, proteinuria, polydipsia and reduced glomerular filtration rate (GFR) and body weight. The activities of urinary prekallikrein (PKLK) and kallikrein (KLK) were reduced accompanied by an up to 3-fold increase of bradykinin (BK) excretion compared to controls. The increased BK excretion suggests that the renal KKS in STZ-diabetes is activated and that the reduction in urinary PKLK and KLK activity may be due to an increased consumption of these enzymes or to a negative feedback mechanism. The stimulation of the renal KKS in STZ-diabetes could reflect an attempt of the organism to balance glomerular hypertension.

Asunto(s)

RESUMEN

Bradykinin (BK) and kallidin (KAL) derivatives containing a Cys residue instead of a Ser residue at positions 6 and 7, respectively [BK(Cys6), KAL(Cys7)], were synthesized. These derivatives were linked to BSA via the Cys residue by a heterobifunctional cross-linker. The coupling product containing a kinin with both free N- and C-terminal ends was used as immunogen. We obtained highly sensitive and specific antisera, simultaneously directed against both free ends. The radioimmunoassay for BK displays a sensitivity of 0.5-60 fmol BK at a dilution of 1:80,000 with 125I-BK(Tyr8) as tracer. Des-Arg9-BK, [BK(1-8)], displayed the highest cross-reactivity in the amount of 24%. Des-Arg1-BK and smaller molecular weight fragments display a cross-reactivity of less than 0.1%. The cross-reactivity of the BK antiserum with KAL is approximately 4%. In presence of 125I-KAL(Tyr9) the radioimmunoassay for KAL displays a sensitivity of 2 to 200 fmol KAL to an antiserum dilution of 1:80,000. The cross-reactivity with BK is 0.02%. KAL(Hyp4), BK(Hyp3), and des-Arg10-KAL [KAL(1-9)] show a cross-reactivity of 6.3, 4.9, and 2.4%. All other natural kinin derivatives show a cross-reactivity of less than 1%. Both assays were used to measure BK and KAL concentrations in blood and urine in humans after extraction and HPLC separation. The BK plasma level 1.97 (SD 0.54) pg/ml. The KAL plasma level is 81.0 (SD 14.3) pg/ml, indicating that KAL instead of BK is a circulating peptide. In urine, the BK level is 16.3 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)