Diethylene glycol poisoning from transcutaneous absorption.

A case of transcutaneous diethylene glycol poisoning with severe acute kidney injury, but a positive outcome, is described. A man without significant medical history was admitted to our hospital due to anuria, gastrointestinal symptoms, and hypertension. Ultrasonography excluded vascular damage and postrenal obstruction. Laboratory tests showed acute kidney injury and metabolic acidosis with increased anion gap; hemodialysis therapy was started. The brother of the patient reported that the patient had been smearing his skin with brake fluid containing diethylene glycol to treat a "dermatitis." Only supportive therapy was given due to the lack of a specific antidote. Continuous venovenous hemofiltration was performed. The kidney biopsy showed acute toxic proximal tubulonecrosis, without deposition of oxalate crystals. His neurologic condition worsened dramatically; supportive care was continued. Over time, acute kidney injury and neurologic damage gradually improved; 33 days after admission, he went to a rehabilitation unit for 5 months, with complete clinical recovery. Historically, diethylene glycol has been the cause of large-scale poisonings from ingestion of contaminated drugs. The clinical evolution is unpredictable. Treatment is not well defined; early hemodialysis treatment reduces levels of toxic metabolites, and fomepizole could be useful in cases with an early diagnosis. A comparison of the characteristics of diethylene glycol versus ethylene glycol poisoning is given.

Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity.

BACKGROUND: Familial renal hypouricemia (RHUC) is a hereditary disease characterized by hypouricemia, high renal fractional excretion of uric acid (FE-UA) and can be complicated by acute kidney failure and nephrolithiasis. Loss-of-function mutations in the SLC22A12 gene cause renal hypouricemia type 1 (RHUC1), whereas renal hypouricemia type 2 (RHUC2) is caused by mutations in the SLC2A9 gene. CASE PRESENTATION: We describe a 24-year-old Pakistani man who was admitted twice to our hospital for severe exercise-induced acute renal failure (EIARF), abdominal pain and fever; he had very low serum UA levels (0.2 mg/dl the first time and 0.09 mg/dl the second time) and high FE-UA (200% and 732% respectively), suggestive of RHUC. Mutational analyses of both urate transporters revealed a new compound heterozygosity for two distinct missense mutations in the SLC2A9 gene: p.Arg380Trp, already identified in heterozygosity, and p.Gly216Arg, previously found in homozygosity or compound heterozygosity in some RHUC2 patients. Compared with previously reported patients harbouring these mutations, our proband showed the highest FE-UA levels, suggesting that the combination of p.Arg380Trp and p.Gly216Arg mutations most severely affects the renal handling of UA. CONCLUSIONS: The clinical and molecular findings from this patient and a review of the literature provide new insights into the genotype-phenotype correlation of this disorder, supporting the evidence of an autosomal recessive inheritance pattern for RHUC2. Further investigations into the functional properties of GLUT9, URAT1 and other urate transporters are required to assess their potential research and clinical implications.

The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors.

BACKGROUND: Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. METHODS AND RESULTS: Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% >70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence. The risk of dialysis and death was 50% lower among those receiving statins. CONCLUSIONS: Clinical features of AERD are identifiable. These make diagnosis possible in most cases. Prognosis is influenced by disease type and severity.

How to manage elderly patients with chronic renal failure: conservative management versus dialysis.

Over the past decade the number of elderly patients reaching end-stage renal disease has more than doubled. A fundamental medical decision that nephrologists commonly have to make is when to start dialytic treatment in elderly patients. Evidence is needed to inform about decision-making for or against dialysis, in particular in those patients frequently affected by multiple comorbidities for which dialysis may not increase survival. In fact, this decision affects quality of life, incurs significant financial costs, and finally mandates use of precious dialysis resources. The negative consequence of initiating dialysis in this group of patients can be deleterious as elderly people are sensitive to lifestyle changes. Furthermore, among dialysis patients, the elderly suffer the highest overall hospitalization and complication rates and most truncated life expectancy on dialysis of any age group. Studies of the factors that affect outcomes in elderly patients on dialysis, or the possibility in postponing in a safe way the start of a dialytic treatment, were lacking until recent years. Recently in the literature, papers have been published that address these questions: the effects of dialysis on morbidity and mortality in elderly patients and the use of a supplemented very low protein diet (sVLPD) in postponing the start of dialysis in elderly. The first study demonstrated that, although dialysis is generally associated with longer survival in patients aged >75 years, those with multiple comorbidities, ischemic heart disease in particular, do not survive longer than those treated conservatively. The second one is a randomized controlled study that compared a sVLPD with dialysis in 112 non-diabetic patients aged >70 years. Survival was not different between the two groups and the number of hospitalizations and days spent in hospital were significantly lower in those on a sVLPD. These studies add to the limited evidence that is currently available to inform elderly patients, their carers and their physicians about the risk and the benefit of dialysis.

Neoral dose adjustment after conversion from C0 to C2 monitoring in stable renal transplant recipients: a prospective single center study.

To determine the clinical impact of conversion from C0 to C2 Neoral monitoring, we conducted a 6-month prospective study in 62 stable renal transplant recipients. Neoral was given alone (19%), with steroids (31%), combined with azathioprine (Aza) or mycophenolate mofetil (MMF) (50%). C0 and C2 target ranges were, respectively, 130-190 and 700-900 ng/mL. Neoral dosages were adjusted according to the C2 range. At baseline, mean C0 and C2 were 157 and 762 ng/mL. After 6 months C0 was 173 ng/mL (p<0.02) and C2 was 804 ng/mL (ns). Although the mean Neoral dose at 6 months was unchanged from baseline, the dose was reduced in 24 patients from 3.6+/-1.2 to 3.0+/-0.9 mg/kg/day, with a mean reduction in serum creatinine (Cr) from 1.4+/-0.4 to 1.3+/-0.3 mg/dL (p<0.001), stable in 8 patients and increased in 30 patients from 3.3+/-1.0 to 3.8+/-1.2 mg/kg/day with no change in serum Cr. Serum transaminases and blood pressure (BP) were unchanged in the three groups. C0 and C2 showed a positive correlation, but with a large dispersion of values (r2=0.14, p<0.001). Overall concordance between the C0 and C2 ranges was 49%. Therefore, in stable transplant patients C0 cannot be considered a C2 surrogate. The conversion from C0 to C2 led to a Neoral dose reduction in approximately 40% of patients with significant improvement in renal function. Most of the remaining patients required an increased dose; however, without an increased incidence of cyclosporin-induced side-effects.

Cholesterol crystal embolic disease in renal allografts.

Cholesterol embolic disease in the renal allograft is not recognized as an important cause of graft dysfunction. We describe here two renal transplant patients with cholesterol embolization in their allograft biopsies. The first, a 48-year-old patient, received a renal transplant from a 62-year-old donor with a history of hypertension and tobacco use. On account of initial non-function, a renal biopsy was taken, which showed acute tubular necrosis and cholesterol emboli. The second, a 55-year-old man, presented chronic allograft failure six years after transplantation; ultrasonography showed a solid renal mass. Nephrectomy specimens revealed renal carcinoma and a combination of chronic rejection and multiple cholesterol emboli. Cholesterol embolic disease is probably an under-reported cause of renal graft dysfunction. The source of the emboli may be either the donor or the recipient's vessels. Since the current tendency is to accept older donors and recipients with more advanced atherosclerotic disease, this condition is likely to become more frequent in the future. Particular care must be taken at the time of organ procurement and during the evaluation of organ donors, in order to reduce the risk of embolization.

Transplantation outcome in patients on PD and HD.

In the past, peritoneal dialysis (PD) has been considered a second choice dialysis modality for many aspects and that negative attitude has been extended also to possible negative effects on renal transplantation. In the last years, many papers have faced the question whether PD could attain similar results in renal transplantation as hemodialysis and there is sufficient evidence to answer that question. On the short time after transplantation, patients coming PD have lower prevalence of delayed graft function than hemodialysis patients, but higher prevalence of renal vascular thrombosis, above all in children. Incidence of acute graft rejection is not different between the two dialysis modalities. The long-term outcome of renal transplantation is similar in patients coming from either PD or hemodialysis.

Steroid-free immunosuppression regime reduces both long-term cardiovascular morbidity and patient mortality in renal transplant recipients.

The aim of this retrospective study was to assess the impact of steroid therapy on cardiovascular disease (CVD) and patient mortality, in 486 on-CsA renal transplant recipients, with a follow-up of 9.5 +/- 4.3 yr. Two hundred and one patients had their steroids permanently withdrawn at sixth month after transplantation (G1); 285 patients did not (G2) as they were unable (acute rejection after suspension) or unsuitable (because of clinical criteria or immunosuppressive protocols). The CVD considered were coronary artery disease diagnosed by angiography and myocardial infarction. G1 and G2 patients were well-matched regarding CVD risk factors, except for age (G1: 44 +/- 14 yr; G2: 40 +/- 12 yr; p < 0.003), incidence of male (G1: 62%; G2: 72%, p < 0.02) incidence of acute rejection (G1: 39%; G2: 83%, p < 0.0001). Both CVD and deaths occurring during the first year of transplantation were excluded from the analysis. At 20 yr, the cumulative probability of developing a CVD, was 3.8% in G1; 23.8% in G2 (p < 0.0005). Patient survival rate was 95% in G1; 62% in G2 (p < 0.003). Mortality caused by CVD was higher in G2 (4.2% vs. 0.5%; p < 0.03). The Cox analysis identified in steroid therapy the main independent risk factors for both CVD (hazard ratio 9.56 p < 0.0001) and patient mortality (hazard ratio 5.99, p < 0.0001). At 10th and 15th year after transplantation, the mean-daily dose of steroids was 4.2 mg. In the long-term, steroid therapy, even in low-doses, increases significantly both the rate of CVD and patient mortality. This retrospective study suggests that steroid-free regime should always be recommended for the prevention of post-transplant CVD. This relevant statement should be followed by a long-term prospective study.