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.

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.

Marcadores de necrose tubular aguda e lesão inflamatória glomerular no sedimento urinária de pacientes com síndrome / Acute tubular necrosis markers and inflammatory glomerular injury urinary sediment syndrome patients

Necrose tubular aguda (NTA) é a causa mais frequente de lesão renal aguda (LRA) em pacientes hospitalizados. Em pacientes com síndrome nefrótica (SNO), a NTA mimetiza, por vezes, quadro de glomerulonefrite rapidamente progressiva e requer instituição precoce de imunossupressores. A análise do sedimento urinário é uma ferramenta não invasiva, de baixo custo e ampla disponibilidade. O achado de células epiteliais no sedimento urinário de pacientes com LRA foi associado ao diagnóstico de NTA. Entretanto, estudos em pacientes com SNO associada são escassos. Técnicas de diagnóstico utilizando sedimento urinário corado normalmente não são utilizadas nesses casos. Além do mais, o sedimento urinário é uma importante fonte de proteínas; estudos proteômicos do sedimento urinário revelaram importantes frações de proteínas não encontradas em sobrenadante, que pode ser usado como potencial biomarcador de LRA. Nosso objetivo é identificar alterações citológicas e protéicas no sedimento urinário que permitam o diagnóstico diferencial entre NTA ou lesão inflamatória-proliferativa glomerular (INF) em pacientes com SNO. Trata-se de um estudo de corte transversal, onde foram incluídos 32 pacientes: 5 pacientes normais (grupo controle), 10 com NTA, 9 sem NTA e 8 com glomerulonefrites exsudativas. As células do sedimento urinário foram contadas, citocentrifugadas, coradas em hematoxilina/eosina ou Papanicolaou e contadas diferencialmente como pequenas (<30μm de diâmetro), médias (30-48μm)...

Acute tubular necrosis (ATN) is the most frequent cause of acute kidney injury (AKI) in hospitalized patients. In patients with nephrotic syndrome (NS), acute tubular necrosis mimic, sometimes, rapidly progressive glomerulonephritis and requires premature institution of immunosuppressive treatment. The analysis of urinary sediment is a noninvasive tool, low cost and wide availability. The found of epithelial cells in the urinary sediment of patients with AKI was associated to ATN diagnosis. However, studies in patients with AKI in the set of NS are scarce. Diagnostics techniques using stained urinary sediment are not ordinarily used in these cases. Furthermore, urinary sediment is an important source of proteins; proteomic studies revealed important fractions of proteins not found in urinary supernatant that could be used as potential biomarkers for AKI. Our goal is identify cytological alterations and protein in urinary sediment which allow the differential diagnosis between ATN and inflammatory-proliferative glomerular lesion (INF) in patients with NS. This is a cross sectional study, in which 32 patients were included: 5 normal patients (control group), 10 with ATN, 9 without ATN and 8 with exudative glomerulonephritis. The cells of urinary sediment were counted, cytocentrifuged, stained of hematoxylin/eosin or Papanicolaou and differentially counted as small (<30μm of diameter), medium (30-48μm)...

The outcome of living related kidney transplantation with multiple renal arteries.

The aim of our study was to compare the surgical complications and short-term outcome of renal transplants with single and multiple renal artery grafts. We reviewed the records of 105 kidney transplantations performed consecutively at our institution from July 2006 to May 2010. The data of 33 (31.4%) renal transplants with multiple arteries were compared with the 72 transplants with single artery (68.6%), and the incidence of surgical complications, post-transplant hypertension, acute tubular necrosis, acute graft rejection, mean creatinine level, and patient and graft survival was analyzed. We further subdivided the study recipients into three groups: group A (n = 72) with one-renal-artery allografts and one-artery anastomosis, group B (n = 6) with multiple-artery allografts with single-artery anastomosis, and group C (n = 27) with multiple-artery allografts with multiple arterial anasatomosis, and compared their outcome. No significant differences were observed among the recipients of all the three groups regarding early vascular and urological complications, post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine level, and graft and patient survival. The mean cold ischemia time in groups B and C was significantly higher (P <0.05). One patient in group A developed renal vein thrombosis resulting in graft nephrectomy. None of the patients with multiple renal arteries developed either vascular or urological complications. In conclusion, kidney transplantation using grafts with multiple renal arteries is equally safe as using grafts with single renal artery, regarding vascular, urological complications, as well as patient and graft survival.

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.

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.

Photosensitisation, crystal-associated cholangiohepatopathy, and acute renal tubular necrosis in calves following ingestion of Phytolacca octandra (inkweed).

CASE HISTORY: In March 2006, an outbreak of photosensitivity affecting 6-8-month-old Friesian heifer calves on a farm in the Rangitikei district of New Zealand was investigated. The calves were grazing wheat stubble paddocks that also had a variety of weeds, especially Phytolacca octandra (inkweed). They also had access to pond water that contained potentially toxic concentrations of the cyanobacteria (blue-green algae) Microcystis and Planktothrix spp. CLINICAL FINDINGS: Initially, affected animals showed acute irritation, agitation, reluctance to walk, recumbency in some animals, hyperaemia of unpigmented skin and jaundice. Serum chemistry revealed elevated liver enzyme activities and azotaemia. Later in the outbreak, exudative dermatitis with formation of crusts on unpigmented skin, dehydration and inappetence were notable signs, as well as occasional diarrhoea. PATHOLOGICAL AND TOXICOLOGICAL FINDINGS: Post-mortem examinations following euthanasia of four severely affected calves and a fifth animal that died naturally revealed livers that were grossly orange brown and mildly enlarged, and kidneys that were enlarged and pale brown. Microscopic lesions in the liver were mild; however, small birefringent crystals in the bile ducts were noted in the first two cases. In contrast, renal lesions were moderate to severe, and included prominent segmental tubular necrosis, granular and cellular casts, and mild interstitial non-suppurative inflammation. In the kidneys of animals examined later in the outbreak, there was early interstitial fibrosis as well as tubular regeneration, with numerous hyaline casts in the renal medulla. Inkweed plants had been heavily browsed, and recognisable portions of the plant were found in the gastrointestinal tracts of affected calves. Chemical analysis of inkweed material revealed triterpene saponins. No known hepatotoxic or nephrotoxic plants were identified in the paddocks. The hepatic lesions were not consistent with published descriptions of cyanobacterial toxicity. Sporidesmin toxicity was ruled out. DIAGNOSIS: Hepatogenous photosensitivity, crystal-associated cholangiohepatopathy, toxic acute renal tubular necrosis, associated with the ingestion of P. octandra, and possibly complicated by cyanobacteria in the water. CLINICAL RELEVANCE: Crystal-associated cholangiohepatopathy with photosensitivity in cattle is rare, and has only been reported in steroidal saponin-containing Brachiaria decumbens poisoning, in Brazil. The consistent pattern of toxic acute renal tubular necrosis was similar to that caused by the ingestion of Quercus, Amaranthus or Lantana spp. A combination of toxicities was conceivable but circumstantial evidence strongly implicated P. octandra. Further toxicological investigation of this plant is warranted before it can be listed as a known nephrotoxin of cattle.

The outcomes of living donor renal transplants with multiple renal arteries: a large cohort study with a mean follow-up period of 10 years.

BACKGROUND: Living donor kidney transplants with multiple arteries are presumed to be associated with an increased risk of complications. OBJECTIVES: The aim of the study was to compare the outcomes in living donor transplantation with the specific intention of comparing long-term outcomes in which the donor kidney had 1 or more renal arteries. The study was undertaken in 2 large transplant centers. METHODS: A retrospective analysis of 201 living donor kidney transplants with multiple arteries that were performed between January 1985 and December 2004 was undertaken. We recorded patient and graft survivals, urological and vascular complications. Kaplan-Meier survival estimates were calculated, and 2-tailed Student t-test was used to compare outcomes. P < .05 was considered statistically significant. RESULTS: Graft and patient survival at 1 year were 93% and 97% and at 5 years were 87% and 92%. The most common complications were vascular (8.9%), followed by urological (6%), acute tubular necrosis (5.5%), and posttransplant hypertension (4.0%). There was significantly higher incidence of acute tubular necrosis (ATN) in multiple-artery transplants. CONCLUSION: In this large cohort of patients studied, apart from a higher incidence of ATN and vascular complications, it appears that the number of renal arteries did not have any adverse impact on the outcomes. The findings from this study suggest that live donor kidneys with multiple renal arteries can be safely utilized for renal transplantation.

Contrast-enhanced sonography in early kidney graft dysfunction.

OBJECTIVES: The aim of this study was a comparison of contrast-enhanced sonography (CEUS) and power Doppler ultrasound (US) findings in renal grafts within 30 days posttransplantation. METHODS: A total of 39 kidney recipients underwent CEUS (SonoVue bolus injection) and US examinations at 5 (T0), 15 (T1), and 30 (T2) days after grafting. The results were correlated with clinical findings and functional evolution. Fourteen patients displayed early acute kidney dysfunction: 10 had acute tubular necrosis (acute tubular necrosis [ATN] group); four acute rejection episodes (ARE group); 25 with normal evolution (as control, C group). Renal biopsies were performed to obtain a diagnosis in the four ATN cases and in all ARE patients. Creatinine and estimated glomerular filtration rate were used as kidney function parameters. CEUS analysis was performed both on cortical and medullary regions while US resistivity indexes (RI) were obtained on main, infrarenal, and arcuate arteries. From an analysis of CEUS time-intensity curves, we computed peak enhancement (PEAK), time to peak (TTP), mean transit time (MTT), regional blood flow (RBF) and volume (RBV), and cortical to medullary ratio of these indies (RATIO). RESULTS: An increased RI was present in the ATN and ARE groups as well as a reduced PEAK and RBF. RATIO-RBV and RATIO-MTT were lower than C among ATN cases, while TTP was higher compared to C in ARE. No statistical difference was evidence for RI between ATN and ARE groups. MTT (T0) was significantly related to creatinine at follow-up (T2). CONCLUSIONS: US and CEUS identified grafts with early dysfunction, but only some CEUS-derived parameters distinguished ATN from ARE, adding prognostic information.

Acute kidney injury in children.

Acute kidney injury (AKI) (previously called acute renal failure) is characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. The incidence of AKI in children appears to be increasing, and the etiology of AKI over the past decades has shifted from primary renal disease to multifactorial causes, particularly in hospitalized children. Genetic factors may predispose some children to AKI. Renal injury can be divided into pre-renal failure, intrinsic renal disease including vascular insults, and obstructive uropathies. The pathophysiology of hypoxia/ischemia-induced AKI is not well understood, but significant progress in elucidating the cellular, biochemical and molecular events has been made over the past several years. The history, physical examination, and laboratory studies, including urinalysis and radiographic studies, can establish the likely cause(s) of AKI. Many interventions such as 'renal-dose dopamine' and diuretic therapy have been shown not to alter the course of AKI. The prognosis of AKI is highly dependent on the underlying etiology of the AKI. Children who have suffered AKI from any cause are at risk for late development of kidney disease several years after the initial insult. Therapeutic interventions in AKI have been largely disappointing, likely due to the complex nature of the pathophysiology of AKI, the fact that the serum creatinine concentration is an insensitive measure of kidney function, and because of co-morbid factors in treated patients. Improved understanding of the pathophysiology of AKI, early biomarkers of AKI, and better classification of AKI are needed for the development of successful therapeutic strategies for the treatment of AKI.

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.

Estrategias inmunosupresoras en receptores añosos / Immunosupressive strategies in elderly recipients

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Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients.

Antiretroviral therapy (ART) has made a significant impact on the morbidity and mortality of patients with HIV infection. However, many of these agents have nephrotoxic potential and are implicated in causing both acute and chronic kidney disease. Safely employing these medications requires a thorough understanding of risk factors that predispose to kidney injury, which include both patient-related characteristics as well drug-related factors. Acute tubular toxicity, crystal nephropathy, and acute interstitial nephritis are among the common renal manifestations of these drugs. Adefovir and tenofovir are associated with tubular toxicity. Crystalluria, crystal nephropathy and nephrolithiasis have been established with indinavir. Acute interstitial nephritis, although not common among antiretroviral agents, is seen with indinavir and atazanavir in these immunocompromised patients. Rarely, enfuvirtide may promote a glomerulopathy. Frequent exposure to other nephrotoxic non-antiretroviral drugs also contributes to kidney disease. Identification and reversal of potentially modifiable risk factors prior to drug administration is important to limiting kidney injury. Recognition of drug-related nephrotoxicity will promote earlier resolution of acute kidney injury and reduce the development of chronic kidney disease.

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.

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.

Tubular and glomerular function in children after renal transplantation.

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.

An improvement in the outcome of acute renal failure.

BACKGROUND: Acute renal failure (ARF) requiring hemodialysis (HD) treatment is related to high mortality. The aim of this study was to analyze the influence of age, disease severity, and catabolism intensity on ARF outcome in patients requiring HD treatment during a 15-year period (1987-2001). METHODS: The retrospective, single-center study included 583 patients, 428 male, 155 female, age 49+/-15 years, treated by intermittent HD using cuprophane membranes with surface area of 1.3 m2. Liano's Acute Tubular Necrosis Individual Severity Score (ATNISS) score and Hypercatabolism Depuration Score (HDS) score were calculated to estimate disease severity and catabolism intensity in ARF patients. RESULTS: Average age of patients significantly increased during the 15-year period for more than one decade (44 to 55 years; p=0.0359), especially during the last five-year period (47+/-14.5 vs. 53+/-14.7, p=0.00015). Disease severity showed significant increase comparing periods 1992-1996 and 1997-2001 (ATNISS 0.385+/-0.197 vs. 0.437+/-0.208; p=0.00137), while catabolism intensity during these periods was similar (HDS 0.569+/-0.145 vs. 0.582+/-0.127; p=0.357). Despite the older and more severely ill population of ARF patients, mortality showed a sustained decrease during the 15-year period. Mortality in the period from 1987 to 1991 (49/83; 59%) was similar with the period 1992-1996 (chi2=0.44, p=0.5081), but significantly higher than in the period 1997-2001 (114/250; 45.6%; chi2=3.98, p = 0.0471). CONCLUSION: The results showed an improvement in the outcome of patients with ARF requiring HD treatment, despite increasing age, disease severity, and use of bioincompatible membranes.