Exposure to Nickel-Cadmium Contamination of Drinking Water Culminates in Liver Cirrhosis, Renal Azotemia, and Metabolic Stress in Rats.

Drinking water polluted by heavy metals has the potential to expose delicate biological systems to a range of health issues. This study embraced the health risks that may arise from subchronic exposure of thirty-four male Wistar rats to nickel (Ni)-cadmium (Cd)-contaminated water. It was done by using the Box-Behnken design (BBD) with three treatment factors (Ni and Cd doses at 50-150 mg/L and exposure at 14-21-28 days) at a single alpha level, resulting in seventeen experimental combinations. Responses such as serum creatinine (CREA) level, blood urea nitrogen (BUN) level, BUN/CREA ratio (BCR), aspartate and alanine aminotransferases (AST and ALT) activities, and the De Ritis ratio (DRR), as well as malondialdehyde (MDA) level, catalase (CAT), and superoxide dismutase (SOD) activities, were evaluated. The results revealed that these pollutants jointly caused hepatocellular damage by raising AST and ALT activities and renal dysfunction by increasing CREA and BUN levels in Wistar rats' sera (p < 0.05). These outcomes were further supported by BCR and DRR values beyond 1. In rats' hepatocytes and renal tissues, synergistic interactions of these metals resulted in higher MDA levels and significant impairments of CAT and SOD activities (p < 0.05). In order to accurately forecast the effects on the responses, the study generated seven acceptable regression models (p < 0.05) with r-squared values of > 80% at no discernible lack of fit (p > 0.05). The findings hereby demonstrated that Wistar rats exposed to these pollutants at varied doses had increased risks of developing liver cirrhosis and azotemia marked by metabolic stress.

RENAL PATHOLOGY IN CAPTIVE ADULT ALAOTRAN GENTLE LEMURS (HAPALEMUR ALAOTRENSIS).

Full medical histories from captive Alaotran gentle lemurs or Bandro (Hapalemur alaotrensis) > 1 yr old that died between 1990 and 2016 were requested from holding institutions. Eighty-six individuals died during the period analyzed. Full postmortem reports were received from 40 (46.5%) animals from 16 different institutions across Europe (15) and North America (1). Eighteen animals (45%) showed azotemia within three months of death, with accompanying histological renal lesions. Another 17 (42.5%) showed histological renal lesions, but no renal function assessment was carried out antemortem, or results were within normal limits. Only five animals (12.5%) showed no renal lesions. Of the 35 (87.5%) animals with histological renal lesions, 18 were females, and 17 were males, 11 were wild caught, and 24 were captive born. Twenty-seven animals were euthanized, seven were found dead, and in one case, no details were provided. Sixty-four blood samples from 22 animals were available. Azotemia was observed on average 407 d antemortem, with a case observed as early as 2,318 d antemortem. Twenty-nine urinalyses from 12 animals were carried out antemortem. All animals showed hematuria or proteinuria in at least one antemortem sample. A pH decrease from 8.5 to 5.0 was observed in two animals antemortem. Gross renal lesions most frequently reported were irregular surface (n = 14), abnormal shape (n = 12), and/or presence of cysts (n = 9). The most common histological lesions were interstitial nephritis (n = 25), interstitial fibrosis (n = 26), tubule dilation (n = 16), and glomerulosclerosis (n = 12). Development of additional diagnostic tools, standardization of ante- and postmortem diagnostic protocols, and further investigation into potential etiologies, such as diets offered in captivity and genetic factors, should be considered as the next steps for the veterinary management of this species in captivity.

Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury.

Angiotensin-converting enzyme inhibitors (ACEi) are effective mitigators of radiation nephropathy. To date, their experimental use has been in fixed-dose regimens. In clinical use, doses of ACEi and other medication may be escalated to achieve greater benefit. We therefore used a rodent model to test the ACEi enalapril as a mitigator of radiation injury in an escalating-dose regimen. Single-fraction partial-body irradiation (PBI) with one hind limb out of the radiation field was used to model accidental or belligerent radiation exposures. PBI doses of 12.5, 12.75 and 13 Gy were used to establish multi-organ injury. One third of the rats underwent PBI alone, and two thirds of the rats had enalapril started five days after PBI at a dose of 30 mg/l in the drinking water. When there was established azotemic renal injury enalapril was escalated to a 60 mg/l dose in half of the animals and then later to a 120 mg/l dose. Irradiated rats on enalapril had significant mitigation of combined pulmonary and renal morbidity and had significantly less azotemia. Dose escalation of enalapril did not significantly improve outcomes compared to fixed-dose enalapril. The current data support use of the ACEi enalapril at a fixed and clinically usable dose to mitigate radiation injury after partial-body radiation exposure.

Hyperammonaemia in four cats with renal azotaemia.

Hyperammonaemia is well reported in animals with advanced hepatic disease and portosystemic shunts, but is unreported in cats with renal disease. This case series describes four cats with severe renal azotaemia in which elevated ammonia levels were detected during the course of treatment. In two cases hyperammonaemia was detected at a time when neurological signs consistent with encephalopathy had developed. This raises the possibility that hyperammonaemia may play a role in the development of encephalopathy in cats with renal azotaemia.

A scoring system to predict renal outcome in IgA nephropathy: from a nationwide prospective study.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis in the world, and a substantial number of patients develop end-stage renal disease (ESRD). Although there are several prognostic indicators, it remains difficult to predict the renal outcome in individual patients. METHODS: A prospective cohort study was conducted in 97 clinical units in Japan from 1995 to 2002. We analysed the data from 2269 patients using proportional hazards models in order to determine the predictors of ESRD in IgA nephropathy and to develop a scoring system to estimate ESRD risk. RESULTS: During the follow-up (median, 77 months), 207 patients developed ESRD. Systolic hypertension, proteinuria, hypoproteinaemia, azotaemia and a high histological grade at initial renal biopsy were independently associated with the risk of ESRD. Mild haematuria predisposed patients to ESRD more than severe haematuria. A scoring system was developed to estimate the 7-year ESRD risk from eight clinical and pathological variables. Actually, this prognostic score accurately classified patients by risk: patients with estimates of 0.0-0.9, 1.0-4.9, 5.0-19.9, 20.0-49.9, and 50.0-100.0% had a 0.2, 2.4, 12.2, 40.2 and 80.8% of ESRD incidence over 7 years, respectively. The corresponding area under the receiver operating characteristic curve was 0.939 [95% confidence interval (CI), 0.921-0.958]. This score was verified in repetitions of the derivation-validation technique. CONCLUSIONS: Although the quality of some data collected by the mail survey is limited and the influence of therapy could not be considered, this scoring system will serve as a useful prognostic tool for IgA nephropathy in clinical practice.