Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during stable transplant function (P<0.001). During acute rejection, serum IL-6 levels increased at least 2 days before plasma creatinine started to rise (P<0.05), indicating its early involvement in the rejection process. During cytomegalovirus (CMV) disease, serum, but not urine, IL-6 levels were higher (P<0.01), and serum neopterin/creatinine values were higher than during stable transplant function, ATN, or acute rejection (P<0.01). No significant differences with stable transplant function occurred during cyclosporin A toxicity. Measurement of serum IL-6 provided a sensitivity of 84% and a specificity of 85% for the diagnosis of acute rejection episodes not coinciding with ATN. All cases of CMV disease could be diagnosed by measurement of serum neopterin/creatinine, which provided a specificity of 73%.     

Effects of Thyroid Function on the Course of Experimental Chronic Renal Failure in Rats

Thyroid hormone has been reported to affect renal function. To investigate the effects of thyroid hormone on the progression of renal deterioration, thyroid hormone (dried thyroid) and an antithyroid drug (thiamazole) were administered to adriamycin (ADR)-induced renal failure rats. The rats were divided into four groups, including 1) ADR-DT, given dried thyroid and thiamazole; 2) ADR-T, given thiamazole; 3) ADR; and 4) control. The survival rate at the end of the study (22 weeks) was 62.5% in ADR-DT group and 100% in ADR-T, ADR, and control groups, respectively. There was a significant difference in the body weight and pulse rate between ADR-DT and ADR-T or ADR groups, except for the pulse rate at week 6 (P < 0.05). The creatinine clearance was greater in the ADR-T group than in the ADR or ADR-DT groups at week 22, and was significantly different between the ADR-T and the ADR-DT groups (P < 0.05). The fractional kidney weight and tubular changes were significantly greater in the ADR-DT group than in the ADR-T or ADR groups (P < 0.05). The interstitial volume was significantly greater in the ADR-DT group than in the ADR-T group (P < 0.05). We therefore conclude that a dried thyroid has an aggravative effect in the tubular changes and relative interstitial volume induced by ADR.     

The detection of chronic heart graft rejection by31P NMR spectroscopy

31 P NMRS) for detecting heart graft rejection after transplantation has been investigated by several researchers, and it has thus been demonstrated to be a valid technique for detecting acute myocardial rejection. In this study, we investigated the value of ³¹P NMRS to assess chronic cardiac allograft rejection. Lewis rat hearts were transplanted into the femoral region of F-344 rat recipients which were treated with cyclosporine, 5 mg/kg body weight, by a daily intramuscular injection for 30 days beginning on the day of transplantation. The control isografts employed Lewis donors and recipients not given cyclosporine. The ratios of phosphocreatine (PCr) to inorganic phosphate (P_i), β-adenosine triphosphate (β-ATP) to P_i, and PCr to β-ATP were monitored using surface coil ³¹P NMRS. ³¹P NMRS was performed 3, 30, and 60 days after transplantation, and the degree of the rejection and arteriosclerosis of the coronary arteries were then assessed histologically. The PCr : P_i and β-ATP : P_i ratios for the allografts demonstrated a significant decrease on postoperative day (POD) 60 from that on POD 30 (PCr : P_i, P < 0.001; β-ATP : P_i, P < 0.01). Although a significant difference existed between the isografts and allografts on POD 60 (PCr : P_i, P < 0.01; β-ATP : P_i, P < 0.01), no significant difference was found in the PCr : β-ATP ratio between the allografts and the isografts. On POD 60, the allografts showed significant graft rejection and arteriosclerotic changes in the coronary arteries. These findings therefore demonstrated the effectiveness of ³¹P NMRS for detecting chronic graft rejection in a rat model. (Received for publication on July 10, 1997; accepted on May 15, 1998)     

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5–8 years. Post-transplant sodium iothalamate clearances (IoCl) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 % (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed. Received: 9 March 1999/Revised: 28 December 2000/Accepted: 11 April 2000     

Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy

FK 506 has been reported to be effective in reversing acute renal allograft rejection that is resistant to steroids and to OKT3. The contribution of FK 506 “rescue” therapy to long-term graft survival has not been determined. We report 23 children transplanted between January 1993 and December 1994, 10 of whom received FK 506 “rescue” therapy. Acute rejection was reversed in 8 of 10, with 7 of the remaining grafts still functioning after a mean follow-up of 10.9±7.8 (SD) months (range 1 – 26 months). The actuarial 1-year graft survival rate was 86% compared with 66% for historical controls (P <0.05). We conclude that FK 506 may provide long-term benefits to children facing allograft loss due to acute rejection. Received August 15, 1995; received in revised form and accepted April 1, 1996     

Dietary Fish Oil Supplements Preserve Renal Function in Renal Transplant Recipients with Chronic Vascular Rejection

The effect of dietary fish oil supplements on renal failureand lipid abnormalities was studied in 14 adult renal transplantrecipients with chronic vascular rejection. The rate of declineof renal function (assessed by studying the slope of reciprocalplasma creatinine plots) slowed significantly during a 6-monthperiod on fish oil supplements compared with the preceding 6-monthcontrol period (slope 1/cr during supplementation –3.6x 10^–5 µmol/l per month compared with –13.5x 10^–5 before, the difference in slope being –9.8x 10^–5, 95% confidence interval (CI) –16.2 x 10^–5,–3.5 x 10^–5, P<0.05). Total plasma triglycerideconcentrations decreased during supplementation (mean change–1.15 mmol/l, 95% CI –1.84, –0.47, P<0.003),but there was no change in total plasma cholesterol concentrationor urinary protein excretion. Platelet function was studiedin nine patients. Platelet aggregation induced by adrenalineand collagen was reduced by fish oils (median change in percent aggregation), adrenaline 2 µmol/ –36% (95%CI –68%, –8%, P<0.05), collagen 1 mg/l, –13%(95% CI –44%, –2%, P<0.05). Platelet thromboxaneA₂ release in response to these agents was also significantlyreduced. These results demonstrate that fish oils preserve residualfunction in renal graft failure due to chronic vascular rejection.     

Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial

One hundred twenty-eight patients with different renal diseasesand chronic renal failure, stratified according to the underlyingdisease, were enrolled in a randomized controlled trial to investigatethe effects on the rate of decline of renal function of twodiets, a controlled protein diet (CPD) of 1 g protein/kg idealbody-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6g protein/kg i.b.w./day, given for 27.1±21.8 months.Dietary compliance was assessed by a dietary questionnaire,dietary interviews and measurement of 24-h urinary urea excretion.At the end of 6 months, actual mean protein intake was higherthan expected (1.06±0.25 g/kg i.b.w./day) in CPD patients,and (0.80±0.21 g/kg i.b.w./day) in LPD patients: valueswere similar at 12 and 18 months after the time of enrollment.The end-point, defined as halving of creatinine clearance, wasreached in 40% of patients on CPD, and in 28.6% of those onLPD (P= 0.038 by comparative life-table analysis). Multivariateregression analysis confirmed that CPD was associated with ahigher risk of progression than LPD, and that two additionalparameters (creatinine clearance at the time of randomizationand average proteinuria during the follow-up) were significantindependent risk factors, even more important than protein intake.     

Long-Term Beneficial Effect of Tacrolimus Conversion on Renal Transplant Recipients

Objective. Acute rejection, chronic allograft nephropathy, and cyclosporine (CsA) toxicity remain serious problems for renal transplant recipients and may lead to graft loss. We retrospectively analyzed 34 patients whose biopsies revealed acute and/or chronic allograft rejection, or CsA nephrotoxicity, and who converted from CsA to tacrolimus. Patients and Methods. From July 1996 through September 2003, CsA was converted to tacrolimus in 34 renal transplant recipients (26 male, 8 female) with renal biopsy at our hospital. Blood pressure and serum creatinine levels were checked monthly and serum cholesterol, triglyceride, and glutamic-pyruvic transaminase (GPT) levels were checked every three months. Results. A consistently stable and better function after conversion was obtained in a significant portion (24, 71%) of patients. A statistically significant decline in serum creatinine and an improvement in the glomerular filtration rate were found at 3 m, 6 m, 12 m, 36 m, and 72 m after tacrolimus conversion. In 85.7% (12/14) of patients with acute rejection and in 35.7% (5/14) of patients with chronic allograft nephropathy (concomitant with acute rejection in 5), improved or stabilized graft function was noted. In addition, the systolic blood pressure and diastolic BP dropped significantly (P< 0.05), while there was no significant change in cholesterol, triglyceride, and GPT levels. Conclusion. The beneficial effect of tacrolimus conversion on patients with acute rejection, chronic allograft nephropathy, or CsA nephrotoxicity was demonstrated in long-term follow up. The improvement in both renal function and blood pressure may be of paramount importance in reducing long-term cardiovascular morbidity and mortality.     

Determination of Clara cell protein urinary elimination as a marker of tubular dysfunction

Clara cell 16-kDa protein (CC16) is a protein expressed primarily by the bronchial cells. It is rapidly eliminated by glomerular filtration, reabsorbed almost entirely, and catabolized in proximal tubule cells. To date, normal values for urinary CC16 in healthy children have not been determined. We have studied 63 pediatric patients (mean age 8.17 ± 3.91 years) and 31 healthy children (control group; mean age 8.83 ± 3.65 years). In the control group, the CC16/creatinine ratio was 1.22 ± 1.52 μg/g. In 16 out of 31 control children, the value of the ratio was zero. Fourteen patients (22.2%) showed a high CC16/creatinine ratio; in contrast, among these same patients, the ratio N-acetyl-β-d-glucosaminidase (NAG)/creatinine was elevated in seven cases (11.1%) and the ratio β2-microglobulin/creatinine was elevated in seven cases (11.1%). The three parameters were in agreement in 51 patients (80.9%). Among the patients, the CC16/creatinine ratio was correlated with both the β2-microglobulin/creatinina ratio (r = 0.76, P < 0.001) and the NAG/creatinine ratio (r = 0.6, P < 0.001). Our findings indicate that CC16 is a good marker of proximal tubular function in childhood. The highest observed values were in children with proximal tubulopathies, in children with chronic renal failure, and in those treated with cyclosporine.     

Early postoperative renal function following renal transplantation surgery: effect of anesthetic technique

Purpose. The use of continuous epidural anesthesia in patients with chronic renal failure is rare and controversial. In this study, we compared the effects of epidural versus general anesthesia on early postoperative renal function in patients who underwent renal transplantation surgery. Methods. Sixty-eight adult patients were prospectively randomized to two groups. Group 1 (n-37) received epidural anesthesia with bupivacaine and fentanyl, and group 2 (n-31) received general anesthesia with nitrous oxide and isoflurane. The patients' renal function was compared both with qualitative scintigraphic analysis (kidney perfusion, concentration, and excretion capabilities) and biochemically [serum sodium, potassium, creatinine, and blood urea nitrogen) (BUN)] within the first postoperative week. Results. Patient demographics were similar in the two groups, and the scintigraphic and biochemical evaluations were also comparable. The time of the first appearance of Tc-99m diethylene triamine pentaacetic acid (DTPA) was within normal limits in 75.7% of patients in group 1 and 61.3% of those in group 2. The number of patients with normal peak/background activity and 20 min/peak activity were 15 (40.5%) and 19 (51.4%), respectively, in group 1, and 12 (38.7%) and 15 (48.4%) in group 2 (P > 0.05 for both). The levels of serum creatinine and urea in both groups decreased within days postsurgery compared with preoperative levels (P < 0.05), but the changes were similar in the two groups (P > 0.05). A similar number of patients in both groups were treated for acute rejection (P > 0.05). Conclusion. Our results demonstrate the safe use of both anesthetic techniques in renal transplantation surgery. Received: December 25, 2000 / Accepted: November 5, 2001     

The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis

Summary It has been debated whether postmenopausal osteoporosis is characterized by high or low bone turnover and whether circulating levels of sex steroids contribute to the occurrence of osteoporotic fractures. We examined 154 70-year-old women with or without osteoporotic fractures, and 178 early postmenopausal women with a “rapid” or a “slow” bone loss. In all participants, we determined markers of bone formation (serum alkaline phosphatase (AP) and serum bone Gla protein (BGP)), markers of bone resorption (fasting urinary calcium/creatinine (FU Ca/Cr) and hydroxyproline/creatinine (FU Hpr/Cr)), and serum estrone (E₁), estradiol (E₂), androstenedione (A), and fat mass. The 70-year-old womenwith osteoporotic fractures had significantly elevated AP (P<0.001), BGP (P<0.001), and FU Hpr/Cr (P<0.001) compared with the groupwithout fractures. In the group of early postmenopausal women, the “rapid” bone losers had significantly increased FU Hpr/Cr (P<0.001) and FU Ca/Cr (P<0.001). E₁, E₂, A, and the fat mass did not differ in the groups with and without osteoporotic fractures, whereas the “rapid” bone losers had significantly lower E₁ (P<0.05), E₂ (P<0.05), and fat mass (P<0.01) than the ‘slow” bone losers. It is concluded that patients with manifest osteoporosis and early postmenopausal women with a rapid bone loss have increased biochemical markers of bone turnover. Moreover, the present study demonstrates that early postmenopausal women with an “excessive” bone loss have significantly decreased serum estrogens, whereas it is not possible to detect low estrogens in women with osteoporotic fractures.     

The effect on renal structure and function of late-life-introduced caloric restriction (CR) in rats

Previous studies have shown that life-long caloric restriction in rats protects the kidneys from age-dependent injury. In this study, we analyzed whether late-life-introduced caloric restriction has a similar effect. The study lasted 12 months. Three groups of animals were analyzed: rats fed “ad libitum” (AD, n = 9), rats on 60% caloric restriction (CR, n = 9), and rats fed “ad libitum” for the first six months of their life then switched to 60% caloric restriction thereafter (LCR, n = 9). At the end of the study kidney function was assessed and kidney samples were analyzed histologically. Serum creatinine and urine albumin were higher in AD than in both CR and LCR (P < 0.001). Creatinine clearance (Cl_cr) corrected for body weight was lowest in AD and comparable in CR and LCR. Similarly Cl_cr corrected for kidney weight was lower in AD than in both CR and LCR (P < 0.05). Severe albuminuria was observed only in AD. In CR and LCR the amount of albumin excreted was comparable (AD vs. CR, P < 0.0001; AD vs. LCR, P < 0.001). In morphometric analysis, the mean size of the glomeruli was higher in AD than in both CR and LCR (P < 0.01). Similar results were found for the mesangial area (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.01) and for mesangial cell counts (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.05). No difference was found between CR and LCR in morphometry. In conclusion, our study indicates that late-life introduction of caloric restriction reverses most of the structural and functional changes observed in the kidneys of “ad libitum”-fed rats.     

Glutathione and Glycine in Acute Renal Failure

Background. Ochratoxin A (OTA) is a nephrotoxic metabolite occurring in foodstuffs. In the last decade, OTA‐induced nephropathy in man and animals have been confirmed by previous literature. The correlation between OTA and the severity of CRI and nephrotic syndrome was also researched. Therefore, this study was designed to determine whether OTA also played an important role in renal insufficiency of patients with chronic renal diseases in Taiwan. Methods. The patients in this study were divided into nonnephrotic syndrome and nephrotic syndrome groups, first, to look for the relation between urine protein and OTA. And then these patients were also divided into six groups: (I) patients with chronic glomerulonephritis; (II) patients with chronic interstitial nephritis; (III) patients with diabetes mellitus; (IV) patients with hypertension; (V) patients with other diseases; (VI) patients with unknown reasons. For all groups, laboratory evaluation of kidney such as serum creatinine, urinary creatinine, creatinine clear rate, urinary protein, and urinary analysis were carried out coupled with determination of ochratoxin A level in urine. Results. Higher levels of OTA were found in patients with nephrotic syndrome. There was a significantly positive correlation (P < 0.001) between 24‐hr OTA and 24‐hr urine protein. On the other hand, the mean excretion of OTA in DM group (group III) was found significantly higher compared to the other groups (P < 0.05). Distinct differences (P < 0.01) were found especially when DM group was compared with patients with chronic glomerulonephritis (group I; P = 0.0019), patients with chronic interstitial nephritis (group II; P = 0.0032) and patients with hypertension (group IV; P = 0.0062). Conclusion. The results could lead to the conclusion that OTA could play an important role in proteinuria of patients with chronic renal diseases in Taiwan. And OTA may play a role in diabetes patients with nephropathy. Further longitudinal study is needed to clarify the role of OTA in diabetic nephropathy.     

Risk factors for chronic rejection in pediatric renal allograft recipients

To determine the risk factors predictive of graft loss from chronic rejection in pediatric renal allograft recipients, we reviewed the collaborative study database of the Société de Néphrologie Pédiatrique which registered 314 grafts from January 1987 to December 1991. Of the 289 grafts analyzed, 71 failed during follow-up, chronic rejection being the most common cause of graft loss (35%). The clinical features of the chronic rejection group (n = 25) were compared with those of the group without failure (n = 218). The variables tested by monovariate analysis were cyclosporine dose at 1 year, donor type, donor and recipient age, and acute rejection episodes. The incidence of graft loss due to chronic rejection was 4% (4/109) in patients who had no acute rejection and 16% (21/134) in those with at least one acute rejection episode (P = 0.002). Donor age (≤5 years) was a risk factor for chronic rejection (P = 0.024). Recipient age and donor type were not significantly different between the chronic rejection group and the control group. Using time-dependent covariates, the risk factors were an acute rejection episode (P = 0.003) and low cyclosporine doses at 1 year (P = 0.02). We conclude that acute rejection and low cyclosporine doses in these pediatric patients were risk factors for graft loss due to chronic rejection. Received 3 April 1995; received in revised form 28 December 1995; accepted 22 March 1996     

Predictors of graft survival at diagnosis of antibody-mediated renal allograft rejection: a retrospective single-center cohort study

Antibody-mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy-proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24 months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P = 0.018 and HR 1.57; P = 0.045) and eGFR slope (beta 0.46; P < 0.001 and beta −5.47; P < 0.001). Cyclophosphamide treatment (6× 15 mg/m²) plus high-dose intravenous immunoglobulins (IVIG) (1.5 g/kg) was superior compared with single-dose rituximab (1× 500 mg) plus low-dose IVIG (30 g) (HR 0.10; P = 0.008 and beta 10.70; P = 0.017) and one cycle of bortezomib (4× 1.3 mg/m²) plus low-dose IVIG (HR 0.16; P = 0.049 and beta 11.21; P = 0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome.     

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 ± 10.8 years; serum creatinine 2.7 ± 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)₂D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)₂D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = −0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)₂D (β = 0.434) was a significant predictor of decreases in total and trabecular BMD (R ² = 0.188, P < 0.01; and R ² = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)₂D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.     

Impact of age on renal graft survival in children after the first rejection episode

Infants are thought to be more immunoreactive and at a greater risk for developing irreversible rejection compared with older children. We investigated this by analyzing patient and graft survival rates, incidence of acute rejection, reversibility of acute rejection, development of a subsequent acute rejection, and incidence of graft loss due to rejection in 154 children (<18 years of age) after primary renal transplantation. Most patients (n = 139) were treated with quadruple immunosuppression (antibody, azathioprine, prednisone, cyclosporine). Treatment of the first acute rejection episode (ARE) consisted of antibody and increased prednisone (68%) or increased prednisone alone (30%), and was not significantly different between the age groups. Transplants were from living donors (LRD) in 80% of cases. Patients were followed for at least 1 year (mean 58±30 months); 68% (105/154) of recipients experienced 1 or more ARE. The incidence of ARE was significantly lower in patients <2 years of age (45%) compared with patients 2 – 5 (76%, P = 0.01), 6 – 12 (78%, P = 0.005), and 13 – 17 (76%, P = 0.009) years of age. There was no significant difference in the 1-, 2- and 5-year patient or graft survival rates, the development of a subsequent acute rejection, or the incidence of graft loss due to acute rejection when analyzed by age group. These data suggest that the impact of an ARE is similar for younger and older children in our population receiving predominantly LRD transplants and quadruple immunosuppression. Received April 25, 1995; received in revised form and accepted January 30, 1996     

Ultrastructural Examination of Glomerular and Tubular Changes in Renal Allografts with Acute Rejection

Acute rejection is the most important threat to transplanted kidneys in the early phase after transplantation. With the advances in renal transplant surgery and immunosuppressive therapies, one-year graft survival rates reached 90%, but long-term graft survival did not improve to a similar degree. To prevent acute rejection more effectively and decrease the risk of chronic nephropathy development, the pathogenesis and effects of acute rejection on renal grafts should be further explored.

This study aimed to examine the glomerular and tubular changes ultrastructurally. Tissues were obtained from 11 renal allografts with acute rejection, fixed in 1% Osmium tetra oxide embedded in Epon. The changes in glomerular basement membrane, podocyte, mesangium, and proximal tubules were examined by electron microscope.

Tubular changes such as tubular basement membrane multi-lamellation, MN and PMN cells in peritubular capillaries, tubular vacuolization, mitochondrial changes (increase in number, alterations in cristae organization, or cristae effacement), and infiltration of tubular epithelium by MN cells (mainly lymphocytes) were found statistically significant (p < 0.01) when compared to those of control group. Some forms of endothelial injury (swelling of endothelial cells or fenestrae loss) were also statistically significant (p < 0.01).

Acute rejection is an important predictor of long-term graft survival, and there may be no clinical clue to make diagnosis easier. Therefore ultrastructural changes may help solve this problem together with molecular studies.     

The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open‐label comparative study

This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open‐label, 12‐month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post‐transplantation, 357 patients were randomized to receive standard‐dose cyclosporine (sCsA, n = 179) or reduced‐dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy‐confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P < 0.001), and creatinine clearance (±SEM; Nankivell method) was significantly higher (57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min, P < 0.001) in patients receiving rCsA versus sCsA at 1 year, respectively. Patient and graft survival exceeded 98% in both groups. No significant differences in infection or malignancy were noted between groups. The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12‐month patient and graft survival, a low incidence of BCAR, and improved renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long‐term renal allograft outcomes.     

C-reactive protein in the monitoring of acute rejection after heart transplantation

Histological examination of endomyocardial biopsy (EMB) is the main technique for rejection surveillance after heart transplantation. This technique is elaborate, inconvenient for the patient, and not without complications. We prospectively analyzed whether the measurement of C-reactive protein (CRP), an acute phase protein that quickly rises when there is inflammation, can serve as a marker for immunological quiescence and as an indicator for withholding EMB. During a 6-month period, CRP was measured in all patients referred for EMB as part of the routine follow-up after heart transplantation. Acute rejection in patients with a follow-up of more than 1 year was rare (1/76). In the majority of cases, EMB was taken within the 1-year post-transplantation (170/246 = 69 %). In 71/170 biopsies (42 %), CRP was ≤ 1; in the other 99/170 (58 %), CRP was ≥ 2. When CRP was ≤ 1, acute rejection was diagnosed in 12/70 cases (17 %). In contrast, acute rejection was found in 28/99 cases (28 %) with CRP ≥ 2 (P = 0.1). Although CRP is elevated more often in the presence of acute rejection, its sensitivity does not allow CRP to replace the routine performance of EMB for monitoring rejection after heart transplantation. We did, however, find a prognostic significance with regard to the effect of rejection treatment: in all acute rejections with a CRP ≤ 3 (n = 11), steroids were effective. Received: 6 January 1998 Received after revision: 7 April 1998 Accepted: 20 April 1998