Evidence that addition of azathioprine improves renal function in cyclosporine-treated patients with allograft dysfunction.

Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6-month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza (-0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/- 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction.

Delayed graft function does not reduce the survival of renal transplant allografts.

BACKGROUND: The aim of the present study was to investigate the effect of delayed graft function (DGF) in graft outcome when adjusted by the presence of acute rejection in the first month after transplantation. METHODS: A total of 437 cadaveric renal transplant patients on cyclosporine and steroids were included in the study. Variables related to donor, recipient, and graft were prospectively collected. RESULTS: The incidence of DGF was 44.4%. When patients dying with a functioning graft were censored, graft survival rates at 1 and 6 years were similar in patients with immediate function to those with DGF, when rejection was not present (96% and 81% vs. 95% and 83%, respectively). Rejection negatively influenced graft survival rates at 1 and 6 years, both in patients with immediate graft function (80% and 73%, P<0.05 vs. no DGF/no rejection) and more deeply in those with associated DGF (77% and 62%, P<0.001 vs. no DGF/no rejection). Rejection was more frequently diagnosed in patients with DGF than in those with immediate graft function (50% vs. 39.9%, P<0.05). Length of hospitalization was longer and the number of needle core biopsies was higher in patients with DGF or rejection. The presence of both complications had an additive effect. CONCLUSIONS: This study showed that DGF did not adversely affect kidney graft survival in patients without rejection. However, it increased the length of hospitalization and the number of graft biopsies, thus increasing the cost of transplantation. Moreover, rejection was more frequent in patients with DGF, and it had a negative impact on graft outcome. Because the association of DGF and rejection gave the poorest outcome, an effort should be made to prevent both complications.

Laryngeal tuberculosis in renal allograft patients.

Laryngeal tuberculosis, although the most common granulomatous disease of the larynx, is a rare form of extrapulmonary tuberculosis, never reported in immunosuppressed allograft recipients. We present two cases of laryngeal tuberculosis in renal transplant patients and a review of the literature. Two women, a 29-year-old and a 60-year-old, each more than 9 years after their cadaveric renal allograft, presented with a 2-week febrile illness with hoarseness and dysphagia, and both were found to have laryngeal tuberculosis by direct laryngoscopy. Although both radiographs were unremarkable, both patients had sputum positive for acid-fast bacilli that subsequently grew Mycobacterium tuberculosis. Clinical response promptly followed institution of isoniazid, rifampicin, and pyrazinamide in each case, although both required threefold increases in daily cyclosporin A dosage to maintain therapeutic levels.

Incidence and prognosis of acute renal failure in older patients.

Few studies have assessed the prevalence and outcome of acute renal failure (ARF) in the elderly. Among 437 ARF cases prospectively studied during a nine-year period in a nephrology department, 152 (35%) occurred in patients over 70 years of age (Group 1). Patients over 70 account for only 10.5% of all hospital admissions in our country, and prevalence of ARF was 3.5 times higher in these patients than in younger people. Acute tubular necrosis (ATN) was diagnosed in 40% of Group 1 and 52% of the younger patients (Group 2) (P less than .05), whereas prerenal ARF was found in 47% and 32%, respectively (P less than .001). Dehydration was the most frequent cause of prerenal ARF in the elderly (51%). The etiological distribution of ATN was similar in both groups, being of multifactorial origin in most cases. Oliguria was present in 49% of ATN in Group 1 and in 66% of Group 2 (P less than .05). There were no significant differences in dialysis needs. Mortality was higher in the elderly in all types of ARF, although differences did not reach statistical significance. Need for dialysis, mechanical respiration, decreased level of consciousness, and hypotension were associated with poor prognosis in both groups. Total recovery from ARF in older persons was less frequent and slower than in younger patients. It may be concluded that patients over 70 years of age are at high risk for developing ARF; nevertheless, age should not be used as a discriminating factor in therapeutic decisions concerning ARF.

Influence of dialysate and membrane biocompatibility on hemodynamic stability in hemodialysis.

The contributions of membrane biocompatibility, dialysate temperature and sodium concentration to hemodynamic stability during hemodialysis were studied in 8 patients with a high incidence of hemodialysis-induced symptomatic hypotension. Patients were treated during 8 different periods, randomly ordered in each case, resulting from the combination of the following: the membrane, either Cuprophan or Polyacrylonitrile; the dialysate temperature, 37 or 35 degrees C, and the sodium concentration, 133 or 139 mmol/l. The incidence of symptomatic hypotension was lower at 35 degrees C in the entire study with either membrane and either sodium concentration. It was also lower with a sodium concentration of 139 mmol/l with either temperature and either membrane. There was a lower incidence of symptomatic hypotension when using Polyacrylonitrile, but this difference was not significant. We conclude that changes in physicochemical parameters of dialysate lead to worth-while improvement of symptomatic hypotension in hemodialysis patients, but membrane biocompatibility seems to play a minor role.

Dipyridamole thallium-201 perfusion imaging for the study of ischemic heart disease in hemodialysis patients.

To assess the usefulness of dipyridamole thallium perfusion imaging in the evaluation of myocardial perfusion in hemodialysis (HD), we studied 29 HD patients divided into three groups: A) 13 patients with clinical angina, B) 8 patients without angina but similar in age, sex, time on HD and hematocrit and C) 8 young asymptomatic patients (mean age 33 +/- 9.7 years). Dipyridamole thallium-201 (Tl-201) perfusion imaging revealed myocardial perfusion defects in 8 patients (61%) from group A, 4 (50%) from group B and 1 (12.5%) from group C. These defects were localized in the inferior, posterior and septal segments of the left ventricle. Abnormal myocardial perfusion was associated with age over 50 years and aortic calcifications (p less than 0.05). Eight patients died within the following four years. All had aortic calcifications (p less than 0.001). Our results show that myocardial perfusion defects are frequent even in non-symptomatic HD patients. This suggests that ischemic heart disease could be more frequent than estimated by clinical symptoms alone. Tl-201 scintigraphy may be a useful non-invasive procedure in cardiological evaluation of HD patients.

Acute cardiovascular effects of intravenous cyclosporine.

The acute effects of intravenous (i.v.) cyclosporine A (CsA) on blood pressure and other haemodynamic parameters were examined in 8 patients with end-stage renal disease on haemodialysis (HD). The study was performed after the mid-week haemodialysis session, when the patients were on their dry body weight. Each patient received an i.v. infusion of 5 mg/kg of CsA in 120 ml of 5% dextrose in water during 2 hours. Heart rate, systolic and diastolic blood pressure (SBP, DBP) were monitored by the Holter system. An echocardiogram (M-mode 2-dimensional and Doppler sonography) was performed using an automatic device (Ultramark 6) before CsA administration, at 30, 60 and 120 minutes during CsA infusion, and at 30 minutes thereafter. SBP, DBP and calculated peripheral vascular resistance (CPVR) increased significantly in respect to basal values at 120 and 150 minutes (SBP: basal 130 +/- 21, 120 min: 136 +/- 20, 150 min: 140 +/- 18, p < 0.05 and p < 0.01, respectively. DBP: basal 80 +/- 9, 120 min: 86 +/- 13, 150 min: 88 +/- 13, p < 0.05 and p < 0.01, respectively. CPVR: basal 1000 +/- 228, 120 min: 1178 +/- 305, 150 min: 1236 +/- 270 dyne/s/cm5, p < 0.01). However, systolic volume (SV) and cardiac output (CO) showed significant decreases from the basal values (SV: basal 103 +/- 29, 120 min: 85 +/- 22, 150 min: 85 +/- 17, p < 0.05. CO: basal 8.2 +/- 2, 120 min: 7.3 +/- 1.1, 150 min: 7 +/- 1.2 l/min, p < 0.05). In conclusion, CsA infusion produces a significant elevation of blood pressure, which seems to be mediated by a direct action on peripheral vascular resistance.

[Diagnostic yield of Echo-Doppler in dysfunction of the grafted kidney]. / Rentabilidad diagnóstica del eco-Doppler en la disfunción del injerto renal.

The study's goal is to analyze the usefulness of Eco-Doppler in the knowledge of renal graft hemodynamics and the description of its dysfunction. 234 examinations were performed in 110 patients. Acceleration, mean rate (MR), maximum systolic rate (MXSR) and minimal diastolic rate (MNDR), as well as resistance index (RI) and pulsatility index (PI) were determined in the external iliac, renal, segmentary, interlobular and arcuate arteries. RI and PI, as well as MXSR and the acceleration are higher in the extra-parenchymatous versus the intra-parenchymatous beds. Peak MR and MNDR values are reached in the renal artery. Termino-lateral to external iliac arterial anastomosis conditions higher MXSRs in the renal artery as opposed to termino-terminal to hypogastric artery (p < 0.05). In the arcuate artery, RI > 0.8 is reached in 51.6% of acute tubular necrosis (ATN), 46.9% of acute rejections (CR), 46.3% of chronic rejection (AR), 21% of grafts with cyclosporin-induced nephrotoxicity (NFX) and 12.5% of normal functioning kidneys isolated chance analysis with Eco-Doppler does not distinguish between AR and ATN. A dysfunctional graft with an RR in the arcuate artery of nearly 9.7 suggests NFX, but AR with interstitial predominance cannot be ruled out.

[Surgical complications in 479 renal transplantations]. / Complicaciones quirúrgicas en 479 trasplantes renales.

Exposition of results obtained from the review of the surgical complications found in a series of 479 renal transplantations performed between 1978 and 1992 in our centre, although some of them lack clinical relevance. There was fluid accumulation in 69 patients, distributed between 31 perirenal haematoma. 17 lymphocele, 13 urinoma, 5 perirenal abscesses and 3 mixed. 27.7% required no action. Frequency of renal rupture was 18 cases, 9 due to acute rejection and 9 to vascular thrombosis. Incidence of urinary obstruction was 4.8% with 5.8% of urinary fistula. With regard to the surgical wound, 9 infections, 7 haematomas, 1 eventration and 1 necrotizing fasciitis were observed. Vascular complications consisted in 10 arterial thrombosis, 10 venous thrombosis, 5 mixed thrombosis and 31 arterial stenosis. Treatment instituted for the various cases, its evolution, and an statistical study of risk factors are illustrated.

[Gastrointestinal complications in renal transplantation]. / Complicaciones gastrointestinales en el trasplante renal.

Seventy-nine gastrointestinal complications in 480 recipients of a renal transplant (RT) (16%) are described. The most frequent complication was high digestive haemorrhage (HDH) (19/480) (2.9%); other complications were: esophagitis, gastroenteritis, diverticulitis, cholecystitis, intestinal tuberculosis, rectal ulcer and colonic polyps. Mortality secondary to gastrointestinal complications was 1.1%. Sixty-seven percent of cases with peptic ulcer developed HDH, an incidence higher than that observed in the general population (20%). Twenty-one percent of transplanted patients with DH had ulcer background. Cholecystitis and diverticulitis were complications with a low incidence (0.2% and 0.6%, respectively) which do not seem to justify aggressive diagnostic and therapeutic manoeuvres prior to the transplant. Prevalence of intestinal tuberculosis in this series (0.4%) was higher to that described in the literature.

[Vascular complications in renal transplantation]. / Complicaciones vasculares en el trasplante renal.

Between the years 1979 and 1992 we a total of 479 renal transplants (RT) were performed. In 62 patients (12.9%) there were some clinically significant vascular complications. These have consisted of: 10 cases of arterial thrombosis (2%); 10 cases of venous thrombosis (2%); 5 cases of arterial and venous thrombosis (1%); 31 cases of arterial stenosis (6.5%); and 6 cases of acute haemorrhage originated at the vascular anastomosis level (1.2%). In all those cases with arterial or venous thrombosis, or both, it was necessary to perform transplantation. The arterial stenosis cases were treated with antihypertensive agents in 13 patients; with endoluminal percutaneous angioplasty (EPA) in other 13 patients and with surgery in 5. Both arterial stenosis and complications from their treatment resulted in 5 transplantations. In all cases with early post-surgical haemorrhage originated at the vascular anastomosis level, a surgical review and suture of bleeding site was performed. A total of 31 grafts (6.5%) were lost as a result of vascular complications.