Pulmonary function in chronic renal failure: effects of dialysis and transplantation.

Many possible pulmonary complications of renal disease have been described, but little is known of their physiological importance or the effects on them of different forms of renal replacement therapy. Four groups were recruited, each containing 20 patients. The groups consisted of patients with chronic renal failure before dialysis (group 1); patients receiving continuous ambulatory peritoneal dialysis, never having received a transplant (group 2); patients receiving haemodialysis, never having received a transplant (group 3); and patients after their first successful cadaveric renal transplant (group 4). All were attending the same regional dialysis and transplant unit. None was known to have clinically important lung or chest wall disease. Flow-volume loops were recorded before and after 400 micrograms of salbutamol, and plethysmographic lung volumes and airway conductance and single breath carbon monoxide transfer factor were measured. Only nine of 80 patients had normal lung function. The reductions in spirometric values were minor. Whole lung carbon monoxide transfer factor was reduced in all groups (mean % predicted with 95% confidence intervals: group 1 81.7% (74-89%); group 2 69.7% (62-77%); group 3 87.5% (80-96%); group 4 82.5% (78-87%]. The values were significantly lower in those having continuous ambulatory peritoneal dialysis (group 2). Residual volume was reduced significantly in the group who had undergone renal transplantation (85.7%, 77-94%). There was no correlation between these changes and smoking habit, age, duration or severity of renal failure, duration of treatment, or biochemical derangement. It is concluded that abnormal lung function is common in renal disease. The main change is a reduction in carbon monoxide transfer that persists after transplantation. The likeliest explanation is that subclinical pulmonary oedema progresses to fibrosis before transplantation. The fibrosis may worsen further to cause the reduced residual volume in the recipients of grafts.     

Effect of dialysis and renal transplantation on autonomic dysfunction in chronic renal failure.

Autonomic functions were evaluated in 25 nondialyzed patients with chronic renal failure and eight controls. Eight patients were reassessed after 6.6 +/- 1.0 weeks of hemodialysis and 12 patients were restudied 24 +/- 4.0 weeks after renal transplantation. In addition, six patients who had been on maintenance hemodialysis for a duration of 21.5 +/- 3.0 weeks were also studied. Autonomic function tests, including blood pressure and heart rate response to sudden loud noise, mental arithmetic, hand immersion in cold water, Valsalva maneuver, change in posture and respiration, were performed using brachial artery cannulation and continuous monitoring by electrocardiogram. Baroreceptor sensitivity slope was determined using bolus injections of phenylephrine. Supine and standing plasma norepinephrine levels were measured. The cold pressor test, response to sudden loud noise and mental arithmetic were normal in nondialyzed patients with chronic renal failure, suggesting an intact efferent sympathetic pathway. The plasma norepinephrine concentration varied widely but the mean value was similar to the control group (P greater than 0.05). Expiration/inspiration ratio, lying/standing ratio, Valsalva ratio and the baroreceptor sensitivity slope were significantly abnormal (P less than 0.001) in nondialyzed patients. This indicates a defective efferent parasympathetic pathway and depressed baroreceptor sensitivity. The blood pressure response to phenylephrine was lower in the uremics, suggesting a reduced end-organ responsiveness to alpha agonists. The presence of hypertension did not affect autonomic function. The heart rate response to standing and the baroreceptor sensitivity were significantly lower (P less than 0.05) in patients who developed hypotension during hemodialysis. Lower baroreflex sensitivity could contribute to hypotension during dialysis. Autonomic functions remained unaltered after short- and long-term dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroendocrinology of chronic renal failure and renal transplantation.

Neuroendocrine activity in normal subjects was compared to patients with chronic renal failure on maintenance hemodialysis (CRF-HD) and to cyclosporine-treated renal transplantation (RT) recipients in an effort to further define the mechanisms underlying their associated fluid, electrolyte, and hemodynamic abnormalities. To evaluate neuroendocrine function in CRF and RT patients, plasma levels of angiotensin II (A-II), vasopressin (AVP), atrial natriuretic peptide (ANP), neuropeptide Y, neuropeptide Y (NPY), epinephrine (E), and norepinephrine (NE) were measured before and after HD and RT. Plasma concentrations of A-II, AVP, ANP, and NPY were significantly elevated in patients with CRF. HD did not produce a significant change in plasma concentrations of AVP, ANP, NPY, E, or NE. NE plasma levels, but not E levels, increased pre- and post-HD. A-II plasma levels were elevated basally in CRF patients and significantly increased following HD. Following RT, plasma levels of A-II, AVP, NPY, and creatinine decreased significantly over the first week, but AVP and NPY did not normalize. Plasma levels of ANP were elevated during the first month, then decreased to normal levels in RT patients. NE levels, but not E levels, were elevated both pre- and post-RT. Despite antihypertensive treatment, the group mean arterial pressure increased post-RT from 100 +/- 4.4 to 116 +/- 3.7 mmHg by POD 6.     

Rights of chronic renal failure patients undergoing chronic dialysis therapy.

The Patient Advocacy Committee of the International Federation of Kidney Foundations (IFKF) has developed a document proposing a set of rights for individuals with end stage renal failure (ESRF). These rights have been approved by the Board of Directors of the IFKF. Twenty rights have been developed and are organized into the following categories: (i) need of treatment and choice of patients; (ii) treatment of ESRF by haemodialysis; (iii) treatment of ESRF by peritoneal dialysis; and (iv) renal transplantation. It is the hope of this Committee and the IFKF that this document will provide a stimulus to more scientific inquiry and discussion as to what rights do patients possess with regard to treatment of chronic kidney disease, regardless of where they live or what may be their economic, social, ethnic or political status.     

Pregnancy in chronic dialysis and after renal transplantation

A female patient gave birth to a child while receiving hemodialysis, six years later, she gave birth to another child after cadavatic renal transplantation. Both children showed normal growth without any congenital defects. During the term of pregnancy after renal transplantation, there was no significant rejection episode, and graft function was stable. It seems rare for a patient to bear children during dialysis and after renal transplantation.     

Treatment of chronic renal failure by blood transfusions

In some forms of chronic renal failure, anaemia may be life-threatening. In the present study a total of 112 blood transfusions were carried out in 56 patients with chronic renal insufficiency accompanied by marked anaemia. Of these patients 20 were given 36 ordinary transfusions and 36 were given 76 exchange transfusions. Of those treated with ordinary transfusions, 10 showed marked improvement, 5 deteriorated and 5 did not respond. Of those treated with exchange transfusions, 17 improved (decreased uraemic intoxication, reduced non-protein nitrogen in the blood, improved general condition). Application of exchange transfusion in terminal stages of the disease (19 cases) was unsuccessful. It is concluded that exchange and ordinary transfusions of warm blood may produce a beneficial therapeutic effect if done in the early stages of chronic renal failure.     

Interleukin-8 in chronic renal failure and dialysis patients

A total of 105 patients participated in this study, including10 with chronic glomerulonephritis with normal renal function(CGN patients), 36 uraemic patients (CRF patients), 19 continuousambulatory peritoneal dialysis patients (CAPD) without peritonitis,three CAPD patients with peritonitis, 37 patients undergoingchronic haemodialysis (HD) divided into short-term HD, 15 patients;medium-term HD, 12 patients; and long-term HD, 10 patients.IL-8 and two other proinflammatory cytokines, IL-6 and TNFweretested using a specific immunoassay. IL-8, IL-6, and TNFc serumlevels were significantly increased in patients with chronicrenal failure compared to their levels in normal individuals(P<0.000l, P<0.05 and P<0.000l respectively). The mostpronounced incre ment in IL-8, IL-6 and TNF serum levels wasobserved in CAPD patients (P<0.000l). CAPD patients withoutperitonitis showed relatively low levels of IL-8 or IL-6 inperitoneal dialysate effluents (PDE), whereas PDE-TNF were notdetectable in almost all patients tested. Patients with peritonitisshowed very high serum and PDE levels of IL-8, IL-6 and TNF.The clinical recovery from peritonitis was characterized bya rapid fall in IL-8, IL-6 and TNF in serum and dialysate. HDpatients showed a significant increase in serum levels of IL-8and also IL-6 and TNFcompared to normal individuals (P<0.05,P<0.05 and P<0.01 respectively). HD duration influencedserum levels of IL-8 and TNF since they were significantly higherin short-term HD patients than medium- or long-term HD patients(respectively P<0.05, P<0.00l for IL-8, and P<0.01,P<0.001 for TNF Pre-HD IL-6 levels were not influenced byHD duration. No major modification of IL-8 serum levels couldbe evinced after and before HD sessions in the short-term group,but concentrations of this cytokine were significantly higherafter HD in medium- and long-term HD patients (P<0.05, P<0.0lrespectively). In contrast, HD session did not influence IL-6and TNF levels. We conclude that the cytokine profile is perturbedin uraemia and during dialysis, and that this should be consideredas an inflammatory status.     

Chronic renal failure, dialysis, and renal transplantation in Anderson-Fabry disease

Anderson-Fabry disease (AFd) is a rare, inherited, x-linked disease characterized by the deficiency of the lysosomal enzymatic alpha-galactosidase A activity (alpha-Gal-A). The enzyme defect leads to progressive accumulation of glycosphingolipids (GL) in all kinds of cells, tissues, organs, and body fluids. The clinical manifestations are very protean, the residual activity of alpha-Gal-A and/or different gene mutations might explain different phenotypes, but as yet these concepts have not been proven. Usually, patients with AFd show 3 clinical phases, more evident in men than in heterozygous women. The first phase (childhood and adolescence) is characterized by myalgia, arthralgia, acroparesthesia, fever, cutaneous angiokeratomas, and corneal opacities. The second phase is characterized mainly by renal involvement. In the third phase, severe renal impairment and involvement of cerebrovascular and cardiovascular systems are present. The progression to end-stage renal disease (ESRD) is common in hemizygous males (3rd-5th decade of life); usually, death occurs because of cerebral and/or cardiovascular complications in patients undergoing chronic dialysis therapies. The survival of patients with AFd in dialysis is better than in diabetic patients, but it clearly is decreased compared with uremic patients with other nephropathies, despite a lower mean age of uremia (50 versus 60 y). The outcome of kidney transplantation is similar to that found in other patients with ESRD, despite controversial issues published in the past. The use of a kidney donor with normal alpha-Gal-A activity in the control of the metabolic systemic disease is unproven. The recurrence of GL deposits in the kidney graft has been documented rarely. The definitive treatment for AFd is enzyme replacement therapy with purified alpha-Gal-A produced by a genetically engineered human cell line or Chinese hamster oocytes: relatively short-term studies have shown a significant treatment effect on clinical outcome measures.     

Neoplasia in patients with chronic renal failure on long-term dialysis.

Out of 67 patients accepted for maintenance dialysis (56 for hemodialysis and 11 for peritoneal dialysis) 47 had not received any form of immunosuppression either in connection with renal transplantation or as part of the therapy for their intrinsic renal disease. Six out of the 47 patients (12.8%) were found to have malignancies which were not directly causing their renal failure. Two patients had carcinomas of the kidney, 2 patients had skin cancers, 1 patient had a carcinoma of the stomach and 1 patient had a carcinoid tumour of the small intestine. This raises the question whether prolongation of uremia by long term dialysis may contribute to the development of malignancy by increasing longevity in the chronically immunosuppressed uremic state.     

Improvement of drug-induced chronic renal failure in lung transplantation.

BACKGROUND: Nephrotoxicity is a frequently encountered adverse effect of calcineurin inhibitors (cyclosporine and tacrolimus)-combined immunosuppressive regimens. METHODS: We have compared the glomerular filtration rate in 14 patients who underwent lung transplantation, before and after replacement of azathioprine by mycophenolate mofetil and reduction of associated calcineurin inhibitors doses. RESULTS: After a mean follow-up of 16+/-4 months with the modified immunosuppressive regimen, the mean glomerular filtration rate increased by 20% with no change in lung function. CONCLUSION: By its strong immunosuppressive effect, mycophenolate mofetil allows the decrease of associated calcineurin inhibitor doses, with subsequent improvement of renal function without jeopardizing the transplanted lung.