Emil Sabbaga

Coronary Angiography Is the Best Predictor of Events in Renal Transplant Candidates Compared With Noninvasive Testing

Abstract—Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (≥70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (≥50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P =0.007) and CA (P =0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with ≥70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P =0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.

O contexto do transplante renal no Brasil e sua disparidade geográfica

The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50% die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of Sao Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.

Pregnancy in Women on Chronic Dialysis

Successful pregnancy outcome is an uncommon occurrence in women requiring chronic dialytic treatment, and the most adequate dialysis therapy in the management of these pregnant patients has not been established. During the period 1988–1995, we estudied the outcome of 17 pregnancies in dialyzed females, with an average age of 28.2±5.9 years (range: 18–38 years). Seven women had adequate urine volume (>800 ml/24 h). Five patients started dialysis after conception and the remaining 12 pregnancies were diagnosed after 6–72 months on dialysis. Fourteen women were maintained on hemodialysis (HD) and 3 on continuous ambulatory peritoneal dialysis (CAPD). The HD schedule was increased to 3 h 5–6 times weekly, and CAPD was increased to six 2-liter exchanges/day. Mean serum urea was 78.6 ± 27.4 mg/dl (range 45–110); serum creatinine was 6.5 ± 3.7 mg/dl (3.3–9.8 mg/dl); and hematocrit was 28.9 ± 3.3 vol% (22–35 vol%). Anemia was partially controlled with rHuEpo in 8 patients. Significant problems were polyhydramnios in 7 cases (5 HD/2 CAPD), oligohydramnios in 1 (HD), gestational diabetes in 2 (CAPD), premature labor with spontaneous abortion at the 19th, 22nd and 28th weeks of gestation (2 HD/1 CAPD), hypertension in 8 (7 HD/1 CAPD), and sterile eosinophilic peritonitis in 1 case (CAPD). Mean gestational age at delivery in 14 successful pregnancies (12 HD/2 CAPD) was 32.3 ± 2.6 weeks (27–36 weeks) and mean baby weight was 1,400.7 ± 579.1 g (range 720– 2,650 g). No congenital fetal abnormality was observed. Respiratory distress was observed in 6 infants, with 2 deaths (1 HD/1 CAPD) in the first week after delivery. In this study, successful pregnancies were reported in 70.6% of dialyzed women with uremia, with hemodialysis having a rate of fetal survival of 78.6% and CAPD with 33.3%.

Intraperitoneal pressure and hernias in children on peritoneal dialysis

Abstract Abdominal wall hernias have been increasingly recognized in patients on continuous ambulatory peritoneal dialysis (CAPD). They are also more frequent in children than in adults. The aim of this study was to determine the influence of intraperitoneal pressure (IPP) on the development of hernias in children on CAPD, and if there was a difference between IPP in children and adults. We studied 14 children aged 11.2±3.2 years, body weight 31.1±9.4 kg, who had undergone CAPD for 16.2±14.4 months. Also, 10 adults were studied, aged 48±18 years, body weight 62.4±13.9 kg, on the CAPD program for 35±27 months. The IPP was measured via a column of dialysate in the peritoneal dialysis line, immediately before the drainage of the peritoneal cavity. The pressure was measured with the patients in the supine position, at the level of the umbilical cicatrix with the zero point located on the mean axillary line. IPP was measured at inspiration and at expiration, and the mean of these two measurements was calculated. The children were divided in two groups : group 1 (n=7) without hernias and group 2 (n=7) with hernias (5 umbilical and 2 inguinal). The IPP of all children was 9.5±2.9 cm H2O. The IPP was 8.1±2.6 and 10.9±2.6 cm H2O in groups 1 and 2, respectively (P=0.003). The instilled volume for test was similar in both groups. The IPP of the adults was 13.8±2.8 cm H2O, which was significantly greater than that of the children (P=0.001). In conclusion, hernia is a common complication in children on CAPD and its prevalence is affected by IPP. Other associated factors may be the presence of anatomically weak sites in the abdominal wall of the children, since IPP is lower in children than in adults.

Anuric Acute Renal Failure Caused by Dextran 40 Administration

Dextran 40 is largely used in clinical medicine as a plasma substitute because of its beneficial effects on the microcirculation and antithrombogenic properties. An unusual adverse reaction of dextran administration is oligoanuric acute renal failure. We report two cases of anuric ARF induced by dextran 40. Diuresis and renal function were quickly resumed after plasma-pheresis treatment. Renal biopsy revealed normal kidneys except for swelling and vacuolation of renal tubules suggestive of osmotic nephrosis.

Polycythemia after Kidney Transplantation

3 patients with renal transplantation who developed polycythemia presented normalization of the hemoglobin levels immediately after nephrectomy of the native kidneys. This observation induced the authors to study the role of the native kidneys in the genesis of polycythemia in recipients of renal allografts. Comparison was made among 32 patients submitted to renal transplantation, with maintenance of native kidneys (group I) and among 31 under the same conditions, but without the native kidneys (group II). Both groups were comparable according to age, sex, rejection crisis incidence and immunosuppressive therapy. It was observed that the hemoglobin levels of group I were significantly higher (p 59Fe), was higher in patients of group I. The authors concluded that the native kidneys are responsible for the observed polycythemia after a kidney transplantation.

Histological outcome of acute cellular rejection in kidney transplantation after treatment with methylprednisolone.

BACKGROUND Several studies comparing the response of acute cellular rejection (ACR) episodes to different corticosteroid regimens have been conducted. However, in most of them, the histological evaluation of the infiltrate and its correlation with clinical response was not studied. The clinical and histological outcomes of 37 episodes of ACR treated with methylprednisolone (MP) were studied, with the aim to determine how long the infiltrate takes to be cleared after therapy. METHODS A total of 37 patients with biopsy-proven ACR were treated with 8 or 16 mg of MP/kg/day. Allograft biopsies were repeated at 5 and 10 days after the end of corticotherapy. Clinical and histological outcomes were compared. RESULTS Six patients were excluded; 15 (48.4%) patients responded to therapy; the mean serum creatinine of these patients reached normal levels in the 2 weeks that followed treatment. Nine patients (60%) of this group had signs of ACR on biopsies done 5 days after corticotherapy, and four (26.7%) maintained them on the 10th day. Among 16 patients with no clinical response, none reached normal serum creatinine levels; 15 (93.7%) had signs of rejection 5 days after treatment and maintained them on the 10th day. Histological signs of ACR disappeared in 73.3% of patients with clinical response 10 days after therapy, but in only 6.3% of patients with no response (P=0.001). CONCLUSIONS Biopsies performed 5 days after treatment show a high incidence of features of ACR; such features take on average 10 days to disappear in nearly 75% of cases with successful therapy with MP.

Reversal of Aluminum-Related Bone Disease after Renal Transplantation

We evaluated the course of severe aluminum-related bone disease (ARBD) after the first year of a successful renal transplantation (RTx) in 11 adult patients. Bone pain and muscle weakness, presented in all patients previously to RTx, subsided, and all were able to walk, even the ones who were confined to wheelchairs. Bone necrosis developed in 6 patients, but none required surgical repair. Serum alkaline phosphatase activity increased 2.5 times the upper normal level, up to the 5th month and then declined to normal levels up the 12th month (p < 0.05). The inverse profile was observed in both serum calcium and phosphorus levels. In bone biopsies, there was a significant decrease in all of the following histomorphometric static parameters: osteoid volume, thickness and surface and also in aluminum surface. Also, there was a significant increase in all the dynamic parameters of mineralization: mineral apposition rate, mineralization surface, bone formation rate and adjusted apposition rate. In conclusion, ARBD remarkably improves after 1 year of successful RTx.

Lymphocyte subsets and Langerhans cells in sun-protected and sun-exposed skin of immunosuppressed renal allograft recipients

BACKGROUND Patients who have received renal allografts experience early aging of the skin, opportunistic infections, and an increased incidence of skin cancer. OBJECTIVE We compared the density of lymphocyte subsets and Langerhans cells in normal-appearing skin of renal allograft recipients without skin cancer at 5 to 6 years (group 1) and 14 years after transplant (group 2) with a matched normal control group. METHODS Biopsy specimens of sun-protected and exposed areas from 18 white, kidney allograft recipients (10 in group 1 and 8 in group 2) with normal renal function and from 10 healthy volunteers were semiquantitatively analyzed for dermal lymphocyte subsets and Langerhans cells. RESULTS There was a statistically significant decrease in all dermal cell elements in the sun-protected skin of both groups of patients who had received grafts. The sun-exposed skin of group 2 also showed a significant decrease of dermal CD4+ and CD8+ lymphocytes, and group 1 had a significant decrease in dermal CD8+ lymphocytes. The dermal CD1a+ cell population in the sun-exposed skin from both grafted groups did not differ from the control group. CONCLUSION Kidney transplant recipients showed dermal depletion of cells related to immune surveillance against tumors even before skin cancer occurred, and this depletion seemed to become more marked with the duration of immunosuppression.

Percutaneous Needle Biopsy of the Renal Allograft Using the Automated Needle System: Evaluation of 87 Procedures

Between April 1991 and February 1992 we obtained 87 percutaneous core needle biopsy specimens from 60 patients with the automatic biopsy gun. In 78 cases (89.7%) enough renal tissue was obtained for histological analysis. Acute rejection was present on 35 biopsies (40.3%) indicating antirejection therapy. No pathological signs of rejection were detected on 43 biopsies (49.4%). In 38 instances (43.7%) biopsy diagnosis differed from clinical presumptive diagnosis, affecting patient management, while in the remainder it was helpful to confirm clinical impressions. The only complication of the procedure was gross hematuria (requiring vesical irrigation in 1 patient). Due to its simplicity and low morbidity rate, renal biopsy with the automated needle system is the procedure of choice for evaluation and management of renal allograft dysfunction.