Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

BACKGROUND: Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. METHODS: Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. RESULTS: Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. CONCLUSIONS: During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Evaluating the incidence and risk factors for developing acute tubular necrosis after percutaneous coronary intervention in the management of coronary artery dissection.

BACKGROUND: Coronary artery dissection is managed primarily conservatively with serial imaging or percutaneous coronary intervention (PCI). Exposure to contrast in either modality could potentially result in acute tubular necrosis (ATN). However, no data compares ATN incidence in these management strategies. This study compares the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. METHODS: A retrospective analysis was performed using data from the National Inpatient Sample database, including patients with coronary artery dissection between 2016 through 2020. We analyzed the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. RESULTS: We found that the odds of developing ATN were 22% lower in patients managed with PCI than those managed conservatively. There was no difference in the in-hospital mortality or hospital length of stay between the two groups but the mortality rate in patients with ATN was double that of those who did not develop ATN in both PCI and conservatively managed groups. CONCLUSIONS: The higher incidents of ATN in patients with coronary dissection being managed with conservative measures compared to PCI suggest that the use of CTA may be harmful. Additionally, persons who developed ATN may have higher mortality. Therefore, more studies in the management of coronary artery dissection need to be done which would allow further steps to be taken to reduce this harm.

The evolution of our knowledge of HIV-associated kidney disease in Africa.

Human immunodeficiency virus (HIV) infection started in Africa circa 1930. South Africa has the highest prevalence rate in the world. Although reports of HIV-associated nephropathy (HIVAN) appeared in the early 1980s, the earliest report from sub-Saharan Africa (SSA) came in 1994. Geographical, socioeconomic, political, and ethical factors have worked in concert to shape the character of HIV disease as it is seen in SSA. Political leaders within SSA have, through their actions, significantly contributed to the incidence of HIV infection. Black females, who often face cultural suppression and disadvantage, have a higher prevalence of HIV than males. Too few studies and outcomes data have bedeviled the statistics in SSA in relation to HIVAN prevalence and its management. Much of what is written is approximation and anecdotal. The largest reliable biopsy series comes from the University of Cape Town, where a workable classification of HIVAN has been developed to enable standardization of terminology. Histologic and clinical prognostic indicators with outcomes have been evaluated using this classification. Patients with HIV who present with acute kidney injury appear to have mainly acute tubular necrosis due to sepsis, dehydration, and nephrotoxic drugs. Since the rollout of combination antiretroviral therapy, the extent of HIV infection and kidney disease continues to be modified and possibly retarded.

Acute tubular necrosis and renal failure in patients with glomerular disease.

Renal failure is common in patients with glomerular disease. Although renal failure may result from the glomerular lesion itself, it is also observed in patients with minimal glomerular alterations. Degenerative changes and necrosis of the tubular epithelium are common findings in kidney biopsies from these patients. The aim of this work is to examine the association between acute tubular necrosis (ATN) and renal failure in patients with glomerulopathy and to estimate the relationship between the degree of ATN and renal failure in these patients. Data on age, sex, presence of nephrotic syndrome, and renal failure were recorded for 149 patients, who underwent a renal biopsy for the diagnosis of glomerulopathy. The biopsies were reviewed, and ATN, when present, was classified as one of four grades depending on its intensity. The mean age of the patients was 21 ± 16 years. Eighty patients (54%) were male, 43 (42%) had renal failure, 104 (72%) had nephrotic syndrome, and 66 (45%) had minimal change disease or focal segmental glomerulosclerosis. ATN was present in 115 (77%) patients. The frequency of renal failure was directly correlated with the intensity of ATN [odds ratio (OR) of 26.0 for patients with grade 2 lesions and OR of 45.5 for patients with grade 3 lesions]. ATN is a common finding in the biopsies of patients with glomerulopathy. The severity of ATN is directly associated with the frequency of renal failure in these patients.

Identification of Factors Associated With Acute Tubular Necrosis Following Kidney Transplant in Northern Mexico: Increased Risk With Cold Ischemia After 8 Hours.

AIM: To identify potential risk factors associated with the incidence of acute tubular necrosis (ATN) following kidney transplant in a sample of patients from northern Mexico. METHODS: Secondary analysis of data extracted from clinical files of patients who underwent a kidney transplant between 2000 and 2017 at Christus Muguerza Hospital in the city of Chihuahua. The final sample with complete data included 485 patients. ATN was diagnosed in 13.2% of patients using pathologic, clinical, and laboratory criteria. Adjusted odds ratio (ORs) with 95% CIs from multivariate binary logistic regression were used to identify predictors of ATN. RESULTS: Only 4 of 21 variables analyzed remained statistically significant in the final adjusted model. Cold and warm ischemia followed time-trend patterns with higher odds with longer ischemia times. For cold ischemia, compared with 0 to 240 minutes, ORs were 1.32 (95% CI, 0.49-3.51) for 241-480 minutes, 4.87 (95% CI, 2.29-10.3) for 481-960 minutes, and 10.0 (95% CI, 2.86-35.0) for > 960 minutes; for warm ischemia, compared with 40 to 59 minutes, these were 6.27 (95% CI, 1.95-20.8) for 60-70 minutes and 10.32 (95% CI, 1.95-54.4) for 71-110 minutes. Hypotension during surgery was associated with a higher chance of ATN (OR, 15.9; 95% CI, 4.97-50.9). When the recipients' age was 30 years or older, the probability also increased significantly (OR, 2.88; 95% CI, 1.09-7.57). The final model fitted well and explained 27% of the probability to develop ATN after a kidney transplant. CONCLUSION: Shortening the duration of ischemia and avoiding hypotension during surgery is essential to prevent ATN following a kidney transplant.

Snakebite nephrotoxicity in Asia.

Snakebites have the highest incidence in Asia and represent an important health problem. Clinical renal manifestations include proteinuria, hematuria, pigmenturia, and renal failure. Nephropathy usually is caused by bites by snakes with hemotoxic or myotoxic venoms. These snakes are Russell's viper, saw-scaled viper, hump-nosed pit viper, green pit viper, and sea-snake. Renal pathologic changes include tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Hemodynamic alterations caused by vasoactive mediators and cytokines and direct nephrotoxicity account significantly for the development of nephropathy. Hemorrhage, hypotension, disseminated intravascular coagulation, intravascular hemolysis, and rhabdomyolysis enhance renal ischemia leading to renal failure. Enzymatic activities of snake venoms account for direct nephrotoxicity. Immunologic mechanism plays a minor role.

Risk of Ischemic Kidney Injury in Patients With Nonarteritic Anterior Ischemic Optic Neuropathy: A Nationwide Population-based Study.

PURPOSE: To investigate the risk of acute tubular necrosis (ATN) in patients with nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Population-based cohort study. METHODS: This is a nationwide, population-based, retrospective study using data from the Korean national health claims database from 2011 through 2015. Patients with NAION and randomly selected control subjects from the entire population of South Korea were enrolled. A log-rank analysis was used to evaluate a risk of ATN in the group of patients with NAION (study group) compared to an age-, sex-, and comorbidities-matched control group. Comorbidities included diabetes, chronic lung disease, congestive heart failure, ischemic stroke, anemia, septic shock, and antibiotic use. A Cox proportional hazards regression analysis with cluster effect was performed to calculate the adjusted hazard ratio (aHR) of ATN. RESULTS: A total of 22 498 patients were included in the study group and 31 475 in the control group. Twenty-six cases of ATN were observed in the NAION group and 11 in the control group. The study group was more likely to have ATN (aHR = 2.55, 95% confidence interval: 1.50-5.91, P = .029) than the control group. Among the 26 newly developed cases of ATN, 13 (50%) occurred in the 0-6 months before/after NAION. CONCLUSIONS: We demonstrated that subjects with NAION are at increased risk of ATN and suggested a possible common mechanistic link between the 2 diseases. These results provide significant evidence that proper patient education and further systemic evaluation of the possibility of ATN development are required in patients with NAION.

Lack of Impact of Hyperchloremia in Brain-Dead Organ Donors on the Onset of Kidney Allograft Function in the Recipients.

BACKGROUND: Hyperchloremia produces renal vasoconstriction and fall in glomerular filtration rate. In 90% of brain-dead organ donors, diabetes insipidus develops, characterized by inappropriate diuresis, hyperosmolality, and hyperchloremia. The aim of this study was to determine the relationship between the serum concentration of chlorides of the donor and the onset of the function of the kidney allograft in the recipient. METHODS: We retrospectively studied 213 donors and kidney allograft recipients. Serum creatinine concentrations and glomerular filtration rates on the 1st, 7th, and 30th days after transplantation of the recipients from hyperchloremic donors were compared with the recipients from normochloremic donors, as well as the incidences of acute tubular necrosis and delayed graft function. RESULTS: On the 1st day, serum creatinine concentrations of the recipients from hyperchloremic and normochloremic donors, respectively, were 448.2 ± 212.1 µmol/L and 502.2 ± 197.8 µmol/L (P = .1), on the 7th day, 168.6 ± 102.6 µmol/L and 196.9 ± 120.6 µmol/L (P = .13), and on the 30th day, 129.4 ± 43.3 µmol/L and 131.8 ± 43.6 µmol/L (P = .73). The differences were statistically significant. The groups also did not differ significantly in glomerular filtration rates and incidences of acute tubular necrosis and delayed graft function. CONCLUSIONS: In this study, no significant correlation between serum chloride concentrations of the organ donors and the onset of the function of kidney allografts in the recipients was found.

Association of high pretransplant sIL-6R plasma levels with acute tubular necrosis in kidney graft recipients.

BACKGROUND: Delayed graft function is primarily caused by acute tubular necrosis (ATN). We studied in renal transplant recipients with posttransplant graft biopsy whether an up-regulated immune system in the recipient immediately before transplantation affects the risk of developing ATN and might be relevant for the pathogenesis of ATN. METHODS: In a retrospective study, we analyzed pretransplant and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin plasma levels in patients with ATN (n=26). Matched patients with acute rejection (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. RESULTS: Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves showed that high pretransplant sIL-6R has a high sensitivity (77%) and high specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be higher in ATN patients than in patients with normal biopsy (P=0.001). Patients with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma levels similar to those of patients with normal biopsy (P=NS). CONCLUSION: High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN.

Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit--a homogeneous population?

INTRODUCTION: Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. METHOD: We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. RESULTS: Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64-5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04-3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60-3.76 [P < 0.001] for all patients combined]). CONCLUSION: The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The three forms of ATN exhibited different clinical characteristics. Mortality was strikingly higher in ischaemic and mixed ATN than in nephrotoxic ATN. Although the type of ATN was not an independent predictor of death, the independent factors related to mortality were different for ischaemic, mixed and all patients combined. These data indicate that the three types of ATN represent different patient populations, which should be taken into consideration in future studies.

Early donor lymph node procurement and local HLA typing reduce cold ischemia time and risk of acute tubular necrosis in cadaveric kidney transplantation.

Prolonged cold ischemia time (CIT) is one of the most common causes of acute tubular necrosis (ATN) with consequent delayed graft function after kidney transplantation. The aim of the study was to analyze the impact of early donor lymph nodes (LN) procurement in combination with local or central HLA typing on CIT, on donor-recipient HLA mismatches, and on the early results of grafts. Two hundred six cadaveric procedures were performed from 2001 to 2004 including 86 cases out of 119 recipients who were matched locally and 60 cases out of 87 recipients who were matched centrally, wherein LN were obtained before kidney harvest. CIT was significantly shorter when LN were obtained before kidney harvesting both in local (13.6 vs 20.6 hours) and central (20.1 vs 27.7 hours) matching (both P < .001). ATN frequency was significantly lower in patients with LN obtained earlier (27.9%) when matched locally versus (35.0%) when matched centrally. Kidney graft function estimated at 12 months was similar in both groups. CIT longer than 19.5 hours predicted ATN occurrence with 57.7% sensitivity and 66.4% specificity. Local matching resulted in shortening CIT compared to central matching (15.5 vs 22.4 hours); however, the mismatch in HLA class I and HLA class II were significantly worse (HLA A + B 2.76 vs 2.45, HLA DR 1.21 vs 0.82). These discrepancies did not significantly influence the frequency of ATN (36.1% vs 40.0%) or the kidney graft function at 12 months.

Double kidney transplantation: initial experience of the Bologna Transplant Center.

AIM: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of the study is to verify the results obtained with double-kidney transplantation in terms of graft and patient survival and complications. METHODS: Between September 2001 and September 2004, 16 double-kidney transplantations were performed in our center. The kidneys were all perfused with Celsior solution and the mean cold ischemia time was 17.6+/-2.7 hours. In all cases a pre-transplant kidney biopsy was performed to evaluate the damage. Immunosuppression was tacrolimus based for all patients. RESULTS: Eight patients had good renal postoperative function while the other eight had acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31.2%; there were two surgical revisions for intestinal perforation. The graft and recipient survival was 78.1% and 100% and 78.1% and 93.7% at 3 and 36 months. CONCLUSIONS: Double-kidney transplantation is a safe way to face the organ shortage. Moreover the score used in this study is useful to determine whether a kidney should be refused or suitable for single or dual-kidney transplantation. The results of our initial experience are encouraging, but this series is too small in number to consent a conclusive statement.

Pretransplant dialysis status and outcome of renal transplantation in North American children: a NAPRTCS Study. North American Pediatric Renal Transplant Cooperative Study.

BACKGROUND: There are no large studies of the effect of pretransplant dialysis status on the outcome of renal transplantation (Tx) in children. This study evaluated the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry data for the outcome of Tx in pediatric patients who either (1) received their transplants preemptively or (2) were maintained on dialysis before receiving their transplants. METHODS: We compared graft survival and patient survival rates, incidence of acute tubular necrosis (ATN), acute rejection episodes, and causes of graft failure in peritoneal dialysis (PD) patients with those maintained on hemodialysis (HD) and those undergoing preemptive Tx (PTx). RESULTS: Primary Tx was performed in 2495 children (59% male; 61% Caucasian; 1090 PD, 780 HD, 625 PTx) between 1/1/1992 and 12/31/1996. The overall graft survival rates of the PD and HD groups were similar, but were less than that of the PTx group (3-year: 82% PD and HD, 89% PTx, overall P = 0.0003). Improved graft survival in the PTx group was present only in recipients of grafts from living donors. There was no difference in the overall patient survival rate at 3 years, or in time to first acute-rejection episodes in the three groups. The incidence of ATN in the first 7 days post-Tx was higher in PD and HD patients than in PTx patients (11% PD and 12% HD vs. 2% PTx, P<0.001; HD vs. PD, P = NS). The major single cause of graft failure in each group was: PD, vascular thrombosis (200%); HD, chronic rejection (27%); PTx, acute and chronic rejection (21% each). CONCLUSION: NAPRTCS data show that graft survival is improved in patients receiving PTx, compared with those receiving PD and HD. Graft loss resulting from vascular thrombosis is more common in children who receive PD than in those receiving HD.

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Posttransplantation acute tubular necrosis: risk factors and implications for graft survival.

Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy. Univariate and multivariate analysis were used to investigate the risk factors for DGF induced by acute tubular necrosis (ATN). Seventy-six patients (29%) had DGF, which was caused by ATN in 70 patients (92.1%) and acute rejection (AR) in 6 patients (7.9%). Therefore, we focused on risk factors and consequences for ATN-induced DGF. In monofactorial analysis, ATN was significantly associated with greater weight and presence of an atheromatous disease in both donor and recipient. Other risk factors for ATN were older age of donor, recipient American Society of Anesthesiology (ASA) physical status category IV, cold ischemia time (CIT), and transplantation using the right kidney. The multivariate analysis showed that donor and recipient weight, donor age, transplantation using the right kidney, preservation in Eurocollins solution, ASA score, and CIT were associated with ATN. The incidence of rejection and renal function were not different at 3 months or 1 and 5 years. ATN is the main cause of DGF in kidney transplant recipients. ATN is caused by donor and recipient vascular background, grafting the right kidney, and CIT. ATN does not appear to have an adverse effect on long-term kidney function.

Acute renal failure syndromes in human immunodeficiency virus infection.

Two major groups of renal complications in human immunodeficiency virus (HIV) disease are a spectrum of disorders that result in potentially reversible acute renal failure, primarily acute tubular necrosis (ATN), and HIV-associated nephropathy (HIVAN), predominantly focal and segmental glomerulosclerosis (FSGS), leading to end-stage renal disease (ESRD). Fluid-electrolyte and acid-base derangements frequently encountered in acquired immune deficiency syndrome (AIDS) are major risk factors for the development of acute renal failure (ARF). HIVAN is an unusual form of poorly responsive glomerular disease characterized by nephrotic syndrome, FSGS, and a rapid fulminant progression to ESRD. ARF syndromes encountered in HIV patients are diverse in nature; many are similar to that in non-HIV subjects, whereas some are more common and unique. In general, HIV disease patients with ARF are younger and much sicker. Although ATN secondary to ischemic and toxic injuries is the commonest ARF syndrome, urinary obstruction is a rare cause of severe renal failure. In many AIDS patients afflicted with complicated infections and multi-organ failure, ATN is a terminal event, whereas in others treated aggressively, ARF is associated with good prognosis. In our large comparative study of severe ARF, recovery of renal function and mortality were determined by patient's general hemodynamic status, and not by the presence or absence of HIV infection. The prognosis of hemolytic uremic and thrombotic thrombocytopenic purpura syndromes often observed in HIV patients is much worse than in non-HIV patients. The syndrome of crystalluria-induced ARF is common, and protease inhibitor induced disease is confined to HIV patients.

Adverse effect of donor vasopressor support on immediate and one-year kidney allograft function.

BACKGROUND: This purpose of this study was to determine if there was a significant difference between the rates of acute tubular necrosis (ATN) and long-term graft survival in renal allografts procured from donors requiring inotropic support (DRIS) and those from donors not requiring inotropic support. METHODS: Eighty-two consecutive cadaveric renal transplant patients were prospectively followed in our local procurement area, the Delaware Valley Transplant Program. Forty-eight patients received organs from DRIS (> 10 mcg/kg per minute of dopamine, dobutamine, epinephrine, and norepinephrine alone or in combination), and 34 did not. RESULTS: Allografts from the non-DRIS group had an immediate function rate of 82.4% and a 1-year function rate of 91.2%. In comparison, the DRIS grafts had an immediate function rate of 58.3% and a 1-year function rate of 72.9%. These differences were statistically significant. The mean serum creatinine in the non-DRIS group was 1.46 +/- 0.58 mg/dl, whereas in the DRIS cohort it was 1.89 +/- 0.93 mg/dl. CONCLUSIONS: Kidneys transplanted from DRIS had significantly (1) poorer immediate function, (2) worse 1-year survival rates, and (3) higher serum creatinine at 1 year. We conclude that recipients receiving organs from donors requiring inotropic support are at a higher risk of developing ATN after surgery and experience reduced 1-year function.

Prevention of OKT3 nephrotoxicity after kidney transplantation.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

Follow-up study of renal transplants by duplex Doppler and gray-scale ultrasound.

In the early postoperative period after renal transplantation 388 follow-up ultrasound examinations were performed in 77 patients. Over a period of 18 months standardized duplex indices (resistive index, pulsatility index) and gray-scale parameters (parenchyma/sinus index; medulla/cortex index) were sampled. These data were correlated retrospectively with clinical and pathological diagnoses. To delineate the individual course of duplex and gray-scale indices during different transplant diseases we created a new parameter: the MID (maximal index difference) which is a result of the difference between the highest index during the phase of renal dysfunction and the lowest index during the phase of normal renal function. This MID, calculated for duplex indices and for the parenchyma/sinus index, indicated significant differences in the behavior of renal transplants during the four main diseases: interstitial rejection, vascular rejection, acute tubular necrosis and Cyclosporine A nephrotoxicity. Using the MIDs, a table of cut-off values was established, which enables to differentiate retrospectively these four transplant complications with a sensitivity of 84% and specificity of 81%. In our opinion consequent follow-up examinations with duplex and gray-scale sonography should be performed, enabling sonography to become a helpful diagnostic instrument in the monitoring of renal transplants.

[The effect of donor conditioning and perioperative management of recipients on the initial and late function of kidney transplants]. / Einfluss von Spenderkonditionierung und perioperativem Management des Empfängers auf die Initial- und Spätfunktion nach Nierentransplantation.

On the basis of 88 consecutive cadaveric renal transplants, multiple variables concerning donor conditioning and perioperative recipient management which may have an influence on the occurrence of acute tubular necrosis (ATN), were analysed and their impact on long-term results assessed. Cold ischaemia time turned out to be the greatest risk factor and was seven hours shorter in patients with good initial function when compared with patients with ATN. Although actual one-year graft survival was similar in both groups, the postoperative course was more complicated in the ATN group and management more onerous. Furthermore, two patients of the initial non-function group died of complications directly related to renal replacement therapy. Seventeen hours cold ischaemia time was associated with more than 80% initial function. This time is sufficient to allow careful tissue typing and organ transportation.