Effect of volume expansion on hemodynamics of the hypoperfused rat kidney.

The hemodynamics of the rat kidney were studied during reduction of renal arterial pressure to 35-40 mm Hg (H), and after volume expansion at that pressure with 0.9% NaCl (IS), 1.7% NaCl (HS), 5% mannitol in 0.9% NaCl (MS), 5% mannitol in water (MW), or 50 mM mannitol + 125 mM NaCl. During H, left renal blood flow (RBF) was 0.8+/-0.1 ml/min. Expansion with IS did not alter RBF, but expansion with HS, MS, MW, and 50 + 125 mM NaCl elevated RBF to 200-250% of hypoperfusion values. Glomerular capillary pressure rose significantly from 15.7+/-0.7 mm Hg during H to 22.3+/-1.1, 24.4+/-0.7, and 26.6+/-0.7 mm Hg following expansion with HS, MS, or MW, respectively. Efferent arteriolar pressure also rose significantly to 6.9+/-0.5, 9.7+/-0.8, and 9.5+/-0.9 mm Hg, respectively. Preglomerular resistance fell to 18-24% of H values, and postglomerular resistance fell to 58-74% of H values after expansion with HS, MS, or MW. Glomerular filtration (GFR) could not be detected during H or after IS expansion. HS and mannitol-containing solutions restored GFR to 0.10+/-0.02-0.15+/-0.02 ml/min, and single nephron glomerular filtration to 6-12 nl/min. Papaverine, acetylcholine, and kinins had no effect on RBF or GFR at a perfusion pressure of 35-40 mm Hg. We conclude that mannitol and HS have the capacity to augment RBF during hypoperfusion by reducing arteriolar resistance. The mechanism of the rise in RBF is uncertain; it may be due to changes in effective osmolality of the extracellular fluid or to a direct action of mannitol on vascular smooth muscle. Other potent vasodilators were ineffective during hypoperfusion. Restoration of GFR occurs as a result of the combined effects of augmented RBF and elevated net filtration pressure.

Outcomes of adult cadaveric renal transplantation in ireland 1986 to 2001.

BACKGROUND: Since the introduction of renal transplantation in the Republic of Ireland in 1964, the number of transplants performed annually has increased from single figures in the 1960s to the current rate of approximately 130 renal transplants per year. Improvements in graft and patient outcomes have been associated with the introduction of the immunosuppressive agent Cyclosporin (CSA) in the mid 1980s. AIMS: The aim of this study was to examine trends in outcomes and factors that influence outcomes for adult kidney transplantation from 1986 to 2001. METHODS: All adult cadaveric kidney transplantations carried out between 1986 and 2001 were included. We separated the transplanted grafts and patients into four time periods; 1986-1989, 1990-1993, 1994-1997, 1998-2001. Graft and patient survival outcomes were compared for the different periods. RESULTS: The one-year kidney graft survival rate increased from 82% during 1986-1989 to 86% during 1998-2001. Patient survival over the four time periods studied has remained stable at approximately 95% at one year. CONCLUSION: We report a significant improvement in kidney graft outcomes over the past 16 years. Patient survival has remained relatively stable during this period.

Renal transplantation in the elderly--the Irish experience.

BACKGROUND: The aim of this paper was to evaluate patient and kidney graft survival rates in renal transplant recipients and compare the outcomes between the different patient age groups. METHODS: A retrospective review of all adult renal transplants performed at Beaumont Hospital between the years 1986-2001 was carried out. Patients were defined as 'elderly' if they were 65 years of age or older and 'younger' if less than 65 years at the time of transplantation. Patient and transplant graft survival rates were analysed for each age group. RESULTS: Data were analysed on 1462 'younger' patients and 105 'elderly' renal transplant recipients. Estimated patient survival at 1, 5 and 10 years were 96%, 87% and 74% in the younger patient group compared to 85%, 59% and 33% in the elderly group. The adjusted graft survival rates (adjusted for death due to other causes and with a functioning graft in situ) for the younger group were 89%, 77% and 64% at one, five and ten years respectively, while for the elderly group, adjusted one, five and ten year survival rates were 89%, 83% and 70% respectively. CONCLUSIONS: Although the elderly have a shorter life expectancy than the younger population they do benefit from renal transplantation similar to the younger recipients.

Lisinopril in the treatment of hypertensive patients with renal impairment.

Lisinopril, a long-acting angiotensin-converting enzyme inhibitor, is excreted unchanged by the kidney. To determine how reduced renal function affects the drug's antihypertensive efficacy and safety, we studied 26 patients with hypertension associated with impaired renal function, having glomerular filtration rates (GFRs) of 60 ml/minute or less. These patients were enrolled in an open trial of 12 weeks' duration. They were given single daily doses of lisinopril, starting with 2.5 mg in patients with a GFR of less than 30 ml/minute, and 5 mg in the other patients. The dose was titrated to a maximum of 40 mg daily according to the blood pressure response. A diuretic was then added if required. Mean sitting and standing blood pressures at four, eight, and 12 weeks of treatment were significantly reduced compared with pretreatment values. The median dose of lisinopril was 10 mg daily (range, 2.5 to 40 mg), and only four patients required the addition of a diuretic. The mean GFR was unchanged during the study (36 +/- 16.4 ml/minute at baseline, 39 +/- 20.8 ml/minute after 12 weeks of treatment). Twenty-five patients completed the study. The one patient withdrew because of nausea and vomiting due to reflux esophagitis, which was probably not drug-related. Another patient had transient angioneurotic edema and continued to receive lisinopril. No clinically significant hematologic or biochemical abnormalities were observed. Sixteen patients continued to receive lisinopril for one year. Blood pressure control and GFR were well maintained throughout. Thus, in a group of patients who are often difficult to treat, lisinopril provided highly effective blood pressure control and was generally well tolerated.

Antihypertensive and renal effects of lisinopril in older patients with hypertension.

The antihypertensive efficacy and safety of lisinopril were assessed in 60 older patients with a mean age of 75 years (range, 65 to 85 years) in a 12-week open study. Mean ( +/- SEM) blood pressure while sitting was reduced from 190/106 +/- 3.3/1.8 mm Hg at entry to 162/89 +/- 3.2/1.6 mm Hg after 12 weeks of treatment (p less than 0.001). There was no significant alteration in heart rate, and postural hypotension did not occur. Mean glomerular filtration rate at entry was 61.6 +/- 3.4 ml/minute and was unchanged after 12 weeks of therapy at 62.2 +/- 3.0 ml/minute. Fourteen patients continued to receive lisinopril for a period of one year. Blood pressure remained controlled throughout and heart rate remained unchanged. There was a significant reduction in mean arterial pressure from 128.8 +/- 1.9 mm Hg to 105.1 +/- 1.5 mm Hg (p less than 0.001). Biochemical parameters remained unaltered. There was a significant increase in renal blood flow (p less than 0.025) and a corresponding reduction in renovascular resistance (p less than 0.001) following long-term therapy with lisinopril. Thus, lisinopril was generally well-tolerated and highly effective in lowering blood pressure in older hypertensive patients, whereas at the same time renal function was not adversely changed.

An analysis of tissue-specific transplantation phenomena in a minor histoincompatibility system.

Tissue-specific differences in immunogenicity were demonstrated following allotransplantation across the same minor histocompatibility barrier (BALB/c----DBA/2). In contrast to the high immunogenicity of fetal pancreas and skin, isolated islets, fetal proislets, and thyroid were weakly immunogenic. These tissue-specific effects were not related to the presence of tissue-specific antigens or the absence of recognizable minor alloantigens from the less immunogenic tissues. There was a strong correlation between tissues that were highly immunogenic and those that contained rich populations of donor leukocytes. The survival of fetal pancreas allografts was significantly improved by pretreating the donor tissue in high-oxygen organ culture and by the preparation of fetal proislets. Using other MHC-compatible strain combinations (B10.D2----BALB/c; BALB/c----B10.D2; C3H.SW----C57/10J) strain-specific effects were observed in the immunogenicity of thyroid allografts. In two of three strain combinations (B10.D2----BALB/c; BALB/c----B10.D2), pretreatment of the donor tissue with cyclophosphamide and organ culture prior to grafting significantly improved graft survival. These findings suggest that donor passenger leukocytes may play an important role in determining the immunogenicity of MHC-compatible allografts.

Cultured thyroid allografts induce a state of partial tolerance in adult recipient mice.

Thyroid allografts (BALB/c) prepared for transplantation by cyclophosphamide pretreatment of the donor, followed by organ culture of donor tissues for 3 weeks in a gas phase of 95% O2-5% CO2 function in normal CBA recipient mice for greater than or equal to 350 days. Up to 100 days post-transplantation, the tissue can be rejected by challenge of the recipient with 10(5) BALB/c peritoneal cells. After prolonged residence in the recipient (greater than 100, less than or equal to 350 days), only a proportion of allografts are rejected when the recipient is challenged with 10(5) followed by 10(6) peritoneal cells of donor origin. Recipients of long-term allografts are partially tolerant of BALB/c tissues. They are hyporesponsive to in vivo challenge with BALB/c spleen cells. However, lymph node cells from these animals respond essentially normally to stimulation with BALB/c spleen cells in vitro. Tolerant recipients will accept a second uncultured BALB/c allograft after a transitory rejection crisis. This crisis is not observed in the primary allograft.

Aluminum-related bone disease. Correlation between symptoms, osteoid volume, and aluminum staining.

In order to correlate symptoms, osteoid volume, and aluminum deposition in bone, 46 methacrylate-embedded biopsy specimens from 26 hemodialysis patients were examined. Osteoid volume was measured using computer-assisted morphometric analysis, and aluminum was detected using the Aluminon stain. Positive staining for aluminum was present in biopsies from 21 patients. Osteoid volume did not correlate with duration of dialysis therapy or ingestion of aluminum hydroxide but displayed a logarithmic relationship with dialysate aluminum exposure. Patients with bone pain at the time of biopsy had a greater degree of hyperosteoidosis than asymptomatic subjects. Osteoid volume in patients with fractures and positive aluminum staining decreased on withdrawal from aluminum-rich dialysate. The Aluminon staining technic is a convenient method of confirming aluminum overload.

Glomerulonephritis after ventriculo-atrial shunt.

We describe five patients with glomerulonephritis (GN) associated with cerebrospinal fluid shunt insertion to relieve hydrocephalus. A ventriculo-atrial (V-A) shunt had been placed on average 12.5 years prior to the diagnosis of nephritis (range 0.5-21 years). Four patients developed membranoproliferative glomerulonephritis (MPGN) with associated hypocomplementaemia. A single patient developed focal proliferative glomerulonephritis. Coagulase-negative staphylococci were cultured in four patients, either from blood or from the shunt. Four patients had their shunts removed, two of whom also received antibiotics. The other patient received antibiotics alone for infective endocarditis due to staphylococcal bacteraemia which originated in the shunt. All patients had substantial renal impairment at the time of diagnosis (GFR, glomerular filtration rate, 20-45 ml/min). There was significant improvement in renal function after appropriate treatment; four of the five patients doubled their GFRs and two patients regained normal function.

Clinical experience with aztreonam in urinary and respiratory tract infections.

Twenty patients with severe infection, 10 of the urinary tract and the other 10 of the respiratory tract, were enrolled in a clinical trial of aztreonam, a new monobactam antimicrobial agent. For the urinary tract infections, the mean duration of treatment was 7 days, with doses ranging from 0.25 to 1.0 g aztreonam intravenously twice daily. Sustained clinical and microbiological cure was achieved in 9 of the 10 patients. In the group with respiratory infections, the mean duration of treatment was 9.3 days, patients receiving 1 g aztreonam intravenously 3-times daily. Initial clinical cure was achieved in 9 of the patients, the tenth showing an incomplete response. However, bacteriological recurrence, related to the persistent nature of the underlying disease, occurred in 6 of the 10 patients during the 1-month follow-up period. The only side-effects were mild, transient biochemical abnormalities which did not require drug withdrawal in any patient.

Implications of colonization of vancomycin-resistant enterococci (VRE) in renal dialysis patients. Learning to live with it?

Vancomycin-resistant enterococci (VRE) commonly colonize, but less frequently infect, debilitated patients, such as those on chronic renal dialysis. The emergence of VRE amongst our cohort of renal replacement therapy patients posed considerable challenges in our attempts to prevent spread. Although 60 of 451 (13%) patients became colonized, only two patients required systemic antibiotics for confirmed or suspected invasive infection. Mortality and inpatient stay was greater in VRE-positive compared with VRE-negative patients (50% versus 10%) and patients who were screened on three or more occasions were likely to remain positive (e.g. 56% of patients screened on six occasions were positive). The application of recommended guidelines for the control of VRE, however, severely disrupted our renal dialysis programme and therefore had to be abandoned. As patients on renal dialysis are more likely to acquire VRE, remain colonized, require antibiotics and require regular inpatient or outpatient care more frequently than other patients, control measures should be adapted to minimize spread but not disrupt important and essential medical services.

Determination of the total protein and triglyceride content of human breast milk on the Synchron CX7 Delta analyser.

BACKGROUND: Premature babies have improved clinical outcomes when fed breast milk with a relatively high protein content. Since there was no convenient way of measuring the macronutrition of breast milk we used our routine laboratory pyrogallol red dye binding method for cerebrospinal fluid microprotein (MTP) and our routine method for serum triglyceride to determine the total protein and triglyceride content of human breast milk. METHODS: The total protein contents of whole and defatted breast milk samples, randomly collected from 115 nursing mothers, analysed using a pyrogallol red dye binding assay on a Synchron CX7 Delta analyser were compared with the total protein contents determined by dry combustion analysis. Triglyceride concentrations, determined on the Synchron CX7 Delta analyser were compared with their respective creamatocrits. RESULTS: Passing and Bablok regression analysis (95% confidence interval) gave the following regression equations: y = 5.98(5.48 to 6.56)x-1.32(-2.02 to -0.73) where y is whole milk MTP (g/L) and x is dry combustion analysis (g/100 g); y = 7.09 (6.54 to 7.78)x-2.44 (-3.46 to -1.67) where y is volume-corrected defatted milk MTP (g/L) and x is dry combustion analysis (g/100 g); y = 7.52 (6.86 to 8.24)x+0.90(-2.42 to 3.37) where y is whole milk triglyceride (mmol/L) and x is creamatocrit (%). CONCLUSION: The Synchron CX7 Delta total protein and triglyceride assays provide practical, rapid and reliable methods for the determination of the macronutrition in human milk.

Chronic occult intra-alveolar hemorrhage: a rare cause of failure to respond to erythropoietin.

Recombinant human erythropoietin (EPO) is an effective and safe therapy for correction of anemia in end-stage renal disease (ESRD). Clinical trials reported to date suggest that EPO improves anemia in over 90% of hemodialysis patients with anemia (Eschbach 1989). Factors which have been identified that appear to inhibit the effectiveness of EPO are infection [Muirhead N et al. 1990], iron deficiency, hyperparathyroidism, aluminium excess [Casati 1991] and persistent GIT bleeding. The development of reticulocytosis in response to EPO in the absence of a rise in hematocrit should alert the clinician to the possibility of either hemolysis or occult blood loss. We present a case in which, despite the development of a reticulocytosis of 5% in response to EPO and the absence of hemolysis, we had difficulty in identifying the presumed source of blood loss.

Rapid recurrence of membranous nephropathy in a related allograft.

A patient with membranous nephropathy (MN) received a renal allograft from his brother. The allograft functioned immediately but nephrotic range proteinuria developed seven days after transplantation in the absence of any signs of rejection. Renal function deteriorated five weeks after transplantation due to ureteric obstruction. Nephrostomy drainage resulted in the return of renal function to normal and demonstrated that the allograft was the source of the nephrotic range proteinuria. An open renal biopsy of the allograft performed at the same time revealed the presence of recurrent MN. The recipient was investigated in an attempt to identify possible humoral immune mechanisms that may explain this very rapid recurrence of MN.

Familial adult medullary cystic disease with spastic quadriparesis: a new disease association.

We present two cases of familial adult medullary cystic disease with spastic quadriparesis, an association not previously described. Previous extrarenal associations of the nephronophthisis-medullary cystic disease complex were reported exclusively in childhood cases. Both patients have undergone successful cadaveric renal transplantation, with no evidence of their renal disease recurring. Further work is needed to elucidate the complex genetics of nephronophthisis.

The management of hydrothorax in continuous ambulatory peritoneal dialysis (CAPD).

Four patients on continuous ambulatory peritoneal dialysis (CAPD) developed large, symptomatic pleural effusions after commencing peritoneal dialysis. Pleuroperitoneal fistula in each case was diagnosed by the presence of a high glucose content in pleural fluid, with a normal corresponding blood sugar, and was confirmed by isotope or contrast peritoneography. Two patients had their effusions drained percutaneously, and then underwent pleural sclerosis with intracavitary tetracycline. Two patients had a thoracotomy performed, of which no fistula was identified in one case, and the other patient underwent pleurectomy. All four patients successfully recommenced CAPD several weeks after therapy, without recurrence of effusions. We conclude that pleuroperitoneal connections associated with CAPD do not mandate cessation of peritoneal dialysis and conversion to maintenance haemodialysis. Definitive diagnosis requires aspiration of pleural effusions for glucose estimation. Contrast or isotopic peritoneography is helpful in localising the fistula, but in our experience did not alter management. Simple sclerotherapy is effective and avoids the need for a formal thoracotomy.

Captopril for refractory hypertension in patients with impaired renal function.

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.

Systemic vasculitis with renal involvement--a review.

Twenty five patients with renal vasculitis presenting over an eight year period were reviewed. Ten had microscopic polyarteritis, 6 classic polyarteritis, 5 overlap syndrome, 2 Churg-Strauss syndrome and 2 Wegener's granulomatosis. Clinical features included hypertension, pulmonary involvement, neurological involvement and arthralgia. Serum creatinine was over 500 umol/l in 13 patients, 10 of whom required dialysis. Visceral angiography was positive in 80% of those studied, Focal and segmental necrotising glomerulonephritis was the commonest renal lesion. Treatment consisted of corticosteroids and cytotoxic agents in most cases. Plasmapheresis was used for rapidly progressive renal failure, severe pulmonary haemorrhage or cerebral vasculitis. Improvement or stabilisation of renal function was seen in 68% of patients treated. There were 4 early deaths and one late death. The diagnosis, histology, treatment and outcome of renal vasculitis is discussed. The importance of early diagnosis and treatment is emphasised in this potentially reversible cause of acute renal failure.

Long term outcome of renal transplantation in the pre cyclosporin era: one centre's experience.

The number of renal transplants has been increasing steadily over the last twenty years. This increase has been associated with a significant improvement in the one year graft and patient survival. However, as survival improves, long term complications are becoming more clinically important. We, therefore, retrospectively reviewed our experience of renal transplantation in 165 patients between January 1970 and December 1980, and describe in detail the complications experienced by those whose grafts functioned for 10 years or longer. The 10 year patient survival rate was 47% and graft survival rate was 30%. The graft survival rate for living related grafts was superior to that of cadaveric grafts. The major cause of mortality in the first year following renal transplantation was infection and in subsequent years, cardiovascular disease predominated. Patients whose grafts functioned for 10 years or more developed a variety of complications including infection, skin cancer and hepatic dysfunction. Clinicians involved in the long term care of the patients need to be aware of these problems and skilled in their management.

Clinical and histopathologic findings in adults with the nephrotic syndrome.

The clinical and histopathologic findings in 225 Irish adults with nephrotic syndrome were reviewed. Membranous nephropathy was the most common lesion found (28%), followed by proliferative glomerulonephritis (17%), and focal sclerosing glomerulonephritis (16%). Minimal change disease was the least frequent cause for idiopathic nephrotic syndrome (12%). The major secondary cause of nephrotic syndrome was amyloidosis (13%). The patients were analysed for the predictive value of the level of renal function, presence or absence of hypertension, and the degree of proteinuria. It was not possible to determine the nature of the underlying lesion giving rise to the nephrotic syndrome using any of these variables. There was also no significant difference between primary and secondary glomerular disease with regard to these factors. It is concluded that renal biopsy remains the only definitive method of establishing the underlying lesion causing idiopathic nephrotic syndrome.