Pregnancy after renal transplantation: impact on graft function.
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Biomedical subjects
Publications and source records attributed to C Jacobs.
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In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-France district, the total population of which is 10660000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Pcr) concentration > or = 200 mumol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Pcr of 447 +/- 214 mumol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Pcr of 425 +/- 185 mumol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and > or = 75 years in 19%. Pcr was 200-399 mumol/l in 54%, 400-599 mumol/l in 25%, 600-799 mumol/l in 12% and > or = 800 mumol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged > or = 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Pcr > or = 300 mumol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Pcr 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mumol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.
There are currently more than 500,000 people on long-term renal dialysis throughout the world, some have been treated for more than 20 years. Despite this major success in the treatment of chronic renal failure, many unsolved problems remain, often leading to controversial debate. Should dialysis be "adequate" or "optimal"? To answer this question results are evaluated on the basis of mid-term and long-term survival rates, morbidity and quality of life criteria including psychological tolerance. While the need for a reliable vascular access and an appropriate dialysis system is obvious for haemodialysis, debate has focused on the optimal dialysis time; total weekly duration under 10-11 hours is sometimes advocated. Nephrologists have emphasized that peritoneal dialysis frees patients from the risk of vascular puncture and the need for anticoagulation while providing better haemodynamic stability. The higher morbidity and risk of infectious complications are however major drawbacks of peritoneal dialysis. Both techniques may require use of recombinant human erythropoietin and daily protein intake of about 1.2 g/kg body weight is mandatory. Despite all the progress made in dialysis concepts and technical applications, several factors may lead to "inadequate" dialysis in some patients. Some, such as insufficient blood flow, are subject to corrective measures, others are cost-related. What is the optimal duration of a dialysis session? How often should dialysers be reused? Are bio-compatible membranes or systems for producing sterile haemodialysis fluid cost-effective? Finally, our understanding of the uraemic toxicity syndrome is still insufficient for a totally satisfactory treatment of renal failure. Further advances in technology and in our understanding of the pathophysiology of renal function and dialysis are needed to reduce morbidity of patients treated for end-stage chronic renal failure and improve their quality of life.
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Between 1982 and 1992, the number of new patients taken yearly onto renal replacement therapy (RRT) increased from 42 to 62 per million population. By December 1992, approximately 22,800 patients (401 per million population) were alive under some mode of RRT. The number of patients aged 15 to 34 years starting RRT slumped from 20% to 11%, whereas that of patients aged > or = 75 years tripled (5% to 15%). The proportion of patients with primary glomerulopathy decreased (25% to 19%) whereas that of patients with vascular diseases or diabetic nephropathy increased notably (14% to 21% and 7% to 13%, respectively). An ever increasing proportion of patients were treated with in-center or limited-care hemodialysis, whereas home hemodialysis steadily declined and continuous ambulatory peritoneal dialysis (CAPD) was applied to 7% of patients in 1991. The average number of weekly hemodialysis hours tended to decrease, particularly for patients aged > or = 75 years. At best, in 1991, approximately 2,000 renal transplants (36 per million population) were performed yearly, but unfortunately, this figure is steadily declining. Five- and 10-year overall survival rates were similar in young patients who were treated with center or home hemodialysis and those who underwent transplantation. Overall survival is rather poor in diabetic patients, 38% and 17% at 5 and 10 years, respectively, but best in those with a functioning first kidney transplant (69% at 10 years). Cardiac causes accounted for one third of all deaths in hemodialysis patients, vascular causes for 15% to 18%, and infectious causes for 10%. Deaths of cardiac or infectious origin were highest in diabetic patients when compared with those recorded in patients with standard (nonsystemic) and vascular renal diseases.
The aim of this study was to evaluate the effects of Ioxaglate on renal haemodynamics and tubular function in renal transplant patients at increased risk of nephrotoxicity. 21 patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate (173 +/- 37 ml) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 ml/min before injection of Ioxaglate were also observed no significant change in mean GFR, ERPF and urinary NAG excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure.
Administration of recombinant human erythropoietin (r-HuEPO) in uraemic pre-dialysis patients is both effective and safe. The benefits are similar to those in dialysis patients: a marked increase in subjective wellbeing and ability to perform physical work. There is a strong argument for treating on the basis of anaemic symptoms, rather than on absolute haematocrit or haemoglobin. Some 30-40% of r-HuEPO-treated pre-dialysis patients may need initiation of, or an increase in, antihypertensive therapy. Provided blood pressure is carefully controlled, r-HuEPO does not appear to accelerate the progression of renal failure, and there is preliminary evidence that it may even delay the need for dialysis in children and possibly in adults. Subcutaneous self-administration is convenient for most pre-dialysis patients; once weekly administration can yield effective results and may enhance patient compliance. As in dialysis patients, detection and correction of iron deficiency play an essential role in maximizing the success of r-HuEPO administration. For most pre-dialysis patients, oral iron administration is convenient, and absorption is satisfactory.
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In enterobacteria, the ampD gene encodes a cytosolic protein which acts as a negative regulator of beta-lactamase expression. It is shown here that the AmpD protein is a novel N-acetylmuramyl-L-alanine amidase (E.C.3.5.1.28) participating in the intracellular recycling of peptidoglycan fragments. Surprisingly, AmpD exhibits an exclusive specificity for substrates containing anhydro muramic acid. This anhydro bond is mainly found in the peptidoglycan degradation products formed by the periplasmic lytic transglycosylases and thus might behave as a 'recycling tag' allowing the enzyme to distinguish these fragments from the newly synthesized peptidoglycan precursors. The AmpD substrate (or substrates) which accumulates in the absence of the corresponding enzymatic activity acts as an intracellular positive effector for beta-lactamase expression and might represent an element of a communication network between the chromosome and the cell wall peptidoglycan.
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We have determined the plasma levels of endothelin-1 (ET-1) in patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis (CAPD). In 10 CAPD patients mean plasma ET levels (7.01 +/- 0.5 pg/ml) were found higher than in normal subjects (3.6 +/- 0.6 pg/ml). Peritoneal clearance of ET-1 was 1.58 +/- 0.12 ml/min and 2.3 +/- 0.2 ml/min during an isotonic peritoneal exchange and a hypertonic exchange, respectively. Plasma ET-1 levels decreased slightly but significantly during a hypertonic 4-hour exchange (from 7.01 +/- 0.5 to 6.14 +/- 0.4 pg/ml) (p < 0.05) and were not modified by an isotonic 4-hour exchange (from 5.7 +/- 0.5 to 6.4 +/- 0.4 pg/ml). ET-1 is known to be an important vascular stimulant and thus elevated ET-1 levels may play a role in the genesis of cardiovascular complications which are the leading cause of mortality in these patients.
Although the acute nephrotoxicity of bone marrow transplantation is well documented, long-term follow-up studies are scanty. Renal function was evaluated in 60 long-term survivors of allogeneic (24 patients) or autologous (36 patients) bone marrow transplantation (BMT) with a mean follow-up of 2 yr. Renal function tests included serum creatinine, GFR (inulin clearance), effective RPF (p-aminohyppurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The mean serum creatinine level was 83 +/- 3 and 93 +/- 3 mumol/L before and after grafting, respectively (P < 0.05). The mean GFR (93 +/- 3 mL/min) and effective RPF (419 +/- 16 mL/min) were significantly lower than in healthy controls (120 +/- 3 and 500 +/- 1 mL/min; P < 0.05) and than in candidates for BMT matched for age and hematologic diseases (117 +/- 3 and 469 +/- 11 mL/min; P < 0.05). Thirty-four patients had a fall in the GFR of at least 20%. Patients who received total body irradiation had significant lower creatinine clearance (86 +/- 3 mL/min) and GFR (86 +/- 3 mL/min) than the controls and the patients who received high-dose chemotherapy (100 +/- 4 and 104 +/- 5 mL/min; P < 0.05). These results suggest that subclinical renal dysfunction occurs frequently in marrow graft recipients, especially those who undergo total body irradiation.
A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
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The number of diabetics with end stage renal failure is growing. The best treatment at the lowest cost possible should be offered to all diabetics if therapeutics facilities are available. Such a policy requires that all dialysis methods and transplantation should be available and that transfer from one method to another should always be allowable. Results observed among diabetics are improving steadily, even in the older age group. However they are inferior to those observed in non diabetic people of the same age. In diabetic patients under fifty years of age, renal transplantation using a kidney from a cadaver or a related donor should be the first choice. In some cases kidney and pancreas transplantation is possible. However, for most patients dialysis methods are required as the only treatment or while waiting for a transplant. If home dialysis is considered, continuous ambulatory peritoneal dialysis offers the opportunity to treat many insulin or non insulin-dependent diabetics at home even those in the high risk population because of age and/or cardio-vascular instability with excellent control of blood glucose levels, hypertension, vision, residual renal function, despite the peritoneal infections. These results are obtained from data in the literature and the survey of patients treated at the Hospital de la Pitié.
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