Role of urine neutrophil gelatinase-associated lipocalin in the early diagnosis of amphotericin B-induced acute kidney injury.

Determination of the neutrophil gelatinase-associated lipocalin (NGAL) level can be used to detect acute kidney injury (AKI) earlier than determination of the serum creatinine (SCr) level in settings such as cardiac surgery, contrast nephropathy, and intensive care units. We hypothesized that urine NGAL (UrNGAL) would be an early biomarker of drug nephrotoxicity. To test this, we studied hemodynamically stable patients treated with amphotericin B (AmB). We measured the SCr and UrNGAL levels at the baseline and daily after initiation of AmB up to day 14 or development of AKI by the use of the SCr criterion. AKI was defined according to a Kidney Disease: Improving Global Outcomes (KDIGO) criterion (an increase in the SCr level by ≥0.3 mg/dl within 48 h or an SCr level ≥1.5 times the baseline level within 7 days). We studied 24 patients with a mean age of 48.4 ± 16.4 years. Most patients were male, and the patients received AmB (12 received AmB deoxycholate and 12 received liposomal AmB) for the treatment of leishmaniasis (91.7%). Overall, 17/24 patients fulfilled a KDIGO criterion for AKI. Peak UrNGAL levels were higher in patients with AKI than in patients without AKI and in recipients of AmB deoxycholate than in recipients of liposomal AmB. The diagnostic performance of the UrNGAL level on day 5 for the detection of AKI was moderate, with the area under the curve (AUC) being 0.68 (95% confidence interval [CI], 0.41 to 0.95). In the subgroup receiving AmB deoxycholate, however, the AUC rose to 0.89 (95% CI, 0.67 to 1.00). In a patient-level analysis, we found that AKI could be detected 3.2 days earlier by the use of the UrNGAL criterion than by the use of the SCr criterion (times to AKI by the UrNGAL and SCr criteria, 3.7 ± 2.5 versus 6.9 ± 3.3 days, respectively; P = 0.001). Future studies should evaluate if a treatment strategy oriented toward evaluation of UrNGAL levels will improve outcomes. These findings for AmB-induced AKI in leishmaniasis patients could serve as a basis for the investigation of urine biomarkers in the early detection of drug nephrotoxicity in other clinical settings.

Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria.

Studies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Here, we used the new Kidney Disease Improving Global Outcome (KDIGO) system to describe the incidence, predictors, and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 with deoxycholate preparation and 42 with liposomal preparation). KDIGO stage 1 requires an absolute increase of ≥0.3 mg/dl or ≥1.5× over baseline serum creatinine (SCr), while stage 2 requires ≥2×, and stage 3 requires ≥3×. A binary KDIGO definition (KDIGObin) corresponds to stage ≥1. For comparison, we included two definitions of AKI traditionally utilized in nephrotoxicity studies: ≥0.5 mg/dl (NT0.5) and ≥2× (NT2×) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (stage 1, 30.9%; stage 2, 18.5%; stage 3, 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and angiotensin-converting enzyme inhibitor (ACE-I). Traditional criteria detected lower incidences of AKI, at 45.1% (NT0.5) and 27.8% (NT2×). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2×). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criterion. However, only traditional criteria were associated with intensive care unit (ICU) admission, mechanical ventilation, and mortality. In conclusion, the increase in sensitivity of KDIGObin is accompanied by a loss of specificity and ability to predict outcomes. Prospective studies are required to weigh the potential gain from early AKI detection against the potential loss from undue changes in management in patients with subtle elevations in SCr.

Neurological symptoms and signs in HTLV-1 patients with overactive bladder syndrome.

OBJECTIVE: To compare neurological symptoms and signs in HTLV-1 asymptomatic carriers and HTLV-1 patients with overactive bladder (OB) syndrome. METHODS: We studied 102 HTLV-1 positive individuals without HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis) divided into two groups according to the presence or absence of OB syndrome. Clinical interview, neurological exam and proviral load was performed in all patients. RESULTS AND CONCLUSIONS: Individuals with OB were more commonly female (84.3 vs. 60.8% of asymptomatics, p=0.01). The prevalence of neurological complaints was higher in OB group, especially hand or foot numbness and arm or leg weakness. There was no difference between the groups in neurological strength and reflexes. Weakness complaint remained strongly associated with OB in multivariate logistic regression analysis adjusting for sex and age [adjusted odds ratio and 95%CI 3.59 (1.45-8.88) in arms and 6.68 (2.63-16.93) in legs]. Proviral load was also different between the two groups with higher level on OB individuals.

Neurological symptoms and signs in HTLV-1 patients with overactive bladder syndrome / Sinais e sintomas neurológicos em pacientes com HTLV-1 e síndrome de bexiga hiperativa

OBJECTIVE: To compare neurological symptoms and signs in HTLV-1 asymptomatic carriers and HTLV-1 patients with overactive bladder (OB) syndrome. METHODS: We studied 102 HTLV-1 positive individuals without HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis) divided into two groups according to the presence or absence of OB syndrome. Clinical interview, neurological exam and proviral load was performed in all patients. RESULTS AND CONCLUSIONS: Individuals with OB were more commonly female (84.3 vs. 60.8% of asymptomatics, p=0.01). The prevalence of neurological complaints was higher in OB group, especially hand or foot numbness and arm or leg weakness. There was no difference between the groups in neurological strength and reflexes. Weakness complaint remained strongly associated with OB in multivariate logistic regression analysis adjusting for sex and age [adjusted odds ratio and 95%CI 3.59 (1.45-8.88) in arms and 6.68 (2.63-16.93) in legs]. Proviral load was also different between the two groups with higher level on OB individuals.

OBJETIVO: Comparar sintomas e sinais neurológicos em pacientes portadores do HTLV-1 assintomáticos e com síndrome de bexiga hiperativa (BH). MÉTODOS: Foram estudados 102 indivíduos com HTLV-1 sem HAM/TSP (mielopatia associada ao HTLV-I/paraparesia espástica tropical), divididos em dois grupos segundo a presença ou ausência de BH. Foram realizados em todos os pacientes entrevista clínica, exame neurológico e carga proviral. RESULTADOS E CONCLUSÕES: Indivíduos com BH foram na maioria do sexo feminino (84,3 vs. 60,8% dos assintomáticos, p=0,01). A prevalência de queixas neurológicas foi maior no grupo BH, especialmente dormências e fraqueza em extremidades. Não houve diferença entre os grupos em relação a achados do exame neurológico. Fraqueza subjetiva permaneceu fortemente associada com BH na regressão logística multivariada ajustada para sexo e idade [OR e IC95% 3,59 (1,45-8,88) nos braços e 6,68 (2,63-16,93) nas pernas]. A carga proviral foi também diferente entre os dois grupos com nível maior em indivíduos com BH.

Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature.

The clinical differentiation between hereditary nonpolyposis colorectal cancer (HNPCC) and attenuated familial adenomatous polyposis (AFAP) is very difficult. The 62-yr-old proband presented with duodenal adenocarcinoma. His history of subtotal colectomy for colon cancer, the rarity of duodenal adenocarcinoma in the general population, and his family history of colon cancer made us suspect that he might have FAP. We investigated this family by obtaining medical records and performing gene analysis. The proband had only 10 adenomatous colon polyps when he underwent subtotal colectomy for the cancer, so classic FAP was excluded. His family history included rectal cancer in his brother at 69 yr of age, colon cancer in his mother at 75 yr, and colon cancer in one maternal cousin at 42 yr. Three months after we started to study this family, the proband's 32-yr-old son presented with rectal cancer. His family fulfilled the Amsterdam criteria for HNPCC, but AFAP could not be excluded. Upon gene testing, the proband was negative for APC gene germline mutation, which made AFAP highly unlikely. Moreover, high microsatellite instability (MSI) was detected in his adenomas and cancer tissues. The fulfillment of Amsterdam criteria, the exclusion of FAP and AFAP, and the high MSI established the diagnosis of HNPCC in this family. We also summarize the differences between FAP, AFAP, and HNPCC; extend the graphic description of the MSI mechanism; and propose a diagnostic strategy for HNPCC.