This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.
Recurrent glomerular disease is an important cause of late allograft loss in renal transplant recipients. Immunoglobulin A nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD) worldwide and its recurrence has been reported in allografts. The present study examined outcomes following renal transplantation (RTX) in 101 patients with ESRD due to biopsy-proven IgAN, in comparison to non-IgA patients, and evaluated the incidence of recurrence. The study population (mean age 34.8 +/- 7.7 years; males 62.2%; Chinese 88.3%) underwent RTX under CsA immunosuppression between November 1984 and December 2004; as two patients underwent retransplantation during the study period, 103 allografts (56.3% cadaveric) were included for retrospective analysis. At time of analysis on 1 January 2005, 78 (75.7%) renal allografts (IgAN RTX) were functioning, of which 51 (49.5%) had normal serum creatinine, 27 (26.2%) had chronic allograft dysfunction, while 25 had graft losses, either due to patient death with functioning grafts (5.8%) or withdrawal to dialysis (18.5%). Persistent microscopic haematuria, not attributable to other causes or proteinuria > 1 g/day occurred in 42.7% and 13.6% of allografts respectively. Of 29 allografts biopsied for evaluation of proteinuria and/or renal dysfunction post-RTX, 8 (27.6%) had IgAN (overall histological recurrence, 7.8%). Of these, three had graft loss due to recurrent IgAN, three had elevated serum creatinine, while two had normal serum creatinine. Overall five and ten year patient survivals for IgAN RTX were 95.3% and 82.2%, and five and ten year actuarial graft survivals were 82.3% and 67.8% respectively. Five and ten year patient and graft survivals for IgAN RTX were not significantly different from that for non-IgAN RTX. In summary, RTX patients with IgAN have a low incidence of documented histological recurrence and recurrence contributing to graft loss occurs in only 2.9%. These results suggest that RTX is an excellent modality of renal replacement therapy in this population.
Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin-angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. However, the ability to reduce angiotensin II response was diminished in diabetic-induced rat kidneys. The effect of angiotensin 1-7 was not inhibited by 1-[(4-(Dimethylamino)-3-methylphenyl] methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate (PD123319), an angiotensin AT(2) receptor antagonist. (D-ALA(7))-Angiotensin I/II (1-7) (D-ALA) (an angiotensin 1-7 receptor antagonist), indomethacin (a cyclo-oxygenase inhibitor), and N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)(a nitric oxide synthetase inhibitor) abolished the attenuation by angiotensin 1-7 in both WKY rats and SHR, indicating that its action is mediated by angiotensin 1-7 receptor that is either coupled to the release of prostaglandins and/or nitric oxide. The vasopressor responses to angiotensin II in mesenteric vasculature bed was also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses to angiotensin II were relatively smaller in SHR but no significant difference was observed between WKY and streptozotocin-induced diabetic rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in WKY, SHR and diabetic-induced mesenteric bed. The attenuation was observed at the lower concentrations of angiotensin II in WKY and diabetic-induced rats but at higher concentrations in SHR. Similar observation as in the renal vasculature was seen with PD123319, D-ALA, and L-NAME. Indomethacin reversed the attenuation by angiotensin 1-7 only in the SHR mesenteric vascular bed. The present findings support the regulatory role of angiotensin 1-7 in the renal and mesenteric vasculature, which is differentially altered in hypertension and diabetes.
Membranous glomerulonephritis (MGN) is one of the common forms of nephrotic syndrome in the adult population. The majority of MGN are idiopathic, but the secondary forms can be seen in the setting of autoimmune disease, neoplasia, infection and following exposure to certain therapeutic agents. Histologically, MGN is an immunologically mediated disease in which immune complexes deposit in the subepithelial space. Syphilis is a venereal disease that can also be acquired by exposure to infected blood. Untreated syphilis may progress and develop renal complications such as membranous glomerulonephritis (MGN) or diffuse endocapillary glomerulonephritis with or without crescent formation. Today, with increasing awareness of sexually transmitted diseases especially HIV infection coupled by the practice of protected sexual intercourse and advancement of medicine, we have seen fewer and fewer cases of acquired syphilis. Furthermore, majority will present with typical syphilitic symptoms of such as chancre, rash, fever and lymph node enlargement in which case the diagnosis is easily obtained. We are reporting a case of acquired syphilis masquerading as membranous glomerulonephritis without typical syphilitic symptoms.
1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.
The Presbytis cristata--Brugia malayi model, now established as a reliable non-human primate model for the experimental screening of potential filaricides, was monitored at monthly intervals for changes in the liver and renal function tests and also for alkaline phosphatase levels during infection. Animals infected with 200-400 infective larvae became patient at 50-90 days post-infection and geometric mean microfilarial counts were above 1000 per ml from the fourth month onwards. There were no significant changes in the biochemical parameters monitored throughout the period of observation. This is an important observation as any changes seen in these parameters during experimental drug studies can be attributed to drug reaction or toxicity and this will be invaluable in decision making as to drug safety.
Four recent cases of dengue fever with severe, unusual clinical manifestations are described. Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal. The two remaining cases showed hepatitis with renal impairment. The significance and importance of these unusual manifestations of dengue disease are discussed.