Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies. METHODS: Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria. RESULTS: NGAL was stable in urine for 7 days when ambient, 4 °C or frozen (-20 or -70 °C). The assay was linear between 0.24 and 10,000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤ 65.0 and ≤ 23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57. CONCLUSIONS: NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.

Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors.

OBJECTIVE: To test the hypothesis that kidney function and metabolic risk factors are associated with glomerular density on renal biopsy samples from healthy adults. PATIENTS AND METHODS: This study compared glomerular density with predonation kidney function, blood pressure, and metabolic risk factors in living kidney donors at Mayo Clinic in Rochester, MN, from May 10, 1999, to February 4, 2009. During implantation of the kidney allograft, an 18-gauge core needle biopsy sample of the renal cortex was obtained, sectioned, and examined by pathologists. Glomerular density was determined by the number of glomeruli (normal and sclerotic) divided by area of cortex. RESULTS: The study sample of 1046 kidney donors had a mean of 21 glomeruli (0.8 sclerotic glomeruli) and a glomerular density of 2.3 glomeruli per square millimeter. In a subset of 54 donors, glomerular density inversely correlated with the mean glomerular area (r(s) = -0.28). Independent predictors of decreased glomerular density were older age, increased glomerular filtration rate, family history of end-stage renal disease, increased serum uric acid, and increased body mass index. Increased urine albumin excretion, hypertension, decreased high-density lipoprotein cholesterol, and metabolic syndrome were also associated with decreased glomerular density after age-sex adjustment. These associations were not explained by the presence of glomerulosclerosis, tubular atrophy, interstitial fibrosis, or arteriosclerosis on the renal biopsy sample. In older donors, decreased glomerular density was attenuated by an increased prevalence of glomerulosclerosis and tubular atrophy. CONCLUSION: Decreased glomerular density is associated with many different kidney function and metabolic risk factors among relatively healthy adults and may represent an early state of increased risk of parenchymal injury.

Renal involvement in Neimann-Pick Disease.

We describe the renal biopsy findings in a 14-year-old girl with Neimann-Pick disease. The renal biopsy showed chronic changes involving all components of the parenchyma, including focal global glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular sclerosis. On light microscopy, significant findings included foamy podocytes, vacuolated tubular epithelial cells and collections of foam cells in the interstitium. Electron microscopy was confirmatory which showed myelin-like inclusions in podocytes, endothelial cells, tubular epithelial cells and small nerves. The findings are similar to Fabry's disease, except that small nerve involvement appears to be unique to Neimann Pick disease.

A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy progresses relentlessly to end-stage renal disease (ESRD). Animal experiments have found that peroxisome proliferator activated receptor-gamma (PPAR-gamma)-based therapy can have a glucose independent effect on renal protection. We hypothesized that PPAR-gamma-based antidiabetic therapy would result in greater reduction in proteinuria compared to sulfonylurea-based therapy. METHODS: In 44 patients with overt diabetic nephropathy, an open-label, blinded end point trial was conducted in which subjects were randomized to either pioglitazone or glipizide to achieve similar glucose control. Proteinuria was assessed by two collections of 24-hour urine samples each month for 4 months. RESULTS: The glipizide group had an adjusted mean increase in proteinuria of 6.1% (95% CI -11.7%, 23.8%), whereas the pioglitazone group had a reduction of 7.2% (95% CI -24.9%, 10.6%). The adjusted reduction with pioglitazone of 13.2% (95% CI -38.4%, 11.9%) was not statistically significant (P= 0.294). Baseline proteinuria, diastolic ambulatory blood pressure, and serum albumin concentration were independent predictors of reduction in proteinuria. The frequency and patterns of adverse events were similar in the two groups. CONCLUSION: In patients with advanced diabetic nephropathy, we found no reduction in proteinuria over 4 months. These data are useful to design larger studies with longer duration of follow-up to demonstrate renal protection of PPAR-gamma agonists.