Distinguishing age-related from disease-related glomerulosclerosis on kidney biopsy: the Aging Kidney Anatomy study.

BACKGROUND: Global glomerulosclerosis is characteristic of chronic kidney disease and also occurs with normal aging. Our goal was to determine the upper limit of normal for number of globally sclerotic glomeruli. METHODS: Core-needle biopsies of the renal cortex were obtained at the time of living kidney transplantation at three centers between 1998 and 2011. The number of globally sclerotic glomeruli was averaged across two biopsy sections. Quantile regression was used to estimate the 95th percentile for globally sclerotic glomeruli as the upper reference limit. There were 2052 donors (mean age 43 years, 41% male, 10% hypertensive), with a mean (SD) of 16.0 (9.7) glomeruli and 0.47 (0.99) globally sclerotic glomeruli on biopsy; only 2.6% had >5% fibrosis. RESULTS: In a multivariable model excluding hypertensive donors, independent predictors of the number of globally sclerotic glomeruli were age, total number of glomeruli and cortex area. A simplified model was used to estimate the 95th percentile for number of globally sclerotic glomeruli by total number of glomeruli and age. For a biopsy section with 17-32 total glomeruli, the 95th percentile ranged from 1 for a 20-year old to 5.5 for a 70-year old donor. Hypertensive donors were more likely to have an abnormal number of globally sclerotic glomeruli (OR = 1.79, P = 0.035). CONCLUSIONS: We have derived the 95% reference limit for number of globally sclerotic glomeruli in ostensibly healthy individuals accounting for age and the biopsy characteristics. Numbers of globally sclerotic glomeruli in a kidney biopsy that exceed these thresholds suggest chronic pathological injury in excess of that expected with normal aging.

Quantification of asymptomatic kidney stone burden by computed tomography for predicting future symptomatic stone events.

OBJECTIVE: To find the optimal characterization of asymptomatic radiographic stone burden on computed tomography (CT) scans. METHODS: A survey was sent to stone formers who underwent a CT scan while asymptomatic during a stone clinic evaluation. Symptomatic stone passage events after CT scan were detected by survey and medical record review. Radiographic stone burden was quantified by number of stones, largest stone diameter, automated total stone volume (TSV), and bilateral stones and then compared as predictors of stone events. RESULTS: There were 550 stone formers; 43% had a stone event for a median of 4.7 years after the CT scan. Stone burden by quartiles was 0-1, 2-3, 4-6, and ≥7 for number of stones; 0-2, 3-4, 5-7, and ≥8 mm for largest stone diameter; and 0-8, 9-78, 79-280, and ≥281 mm(3) for TSV; 48% had bilateral stones. The hazard ratios (HRs) for symptomatic event was 1.30 (P <.001) for the number of stones per quartile, 1.26 (P <.001) for largest stone diameter per quartile, 1.38 (P <.001) for TSV per quartile, and 1.80 (P <.001) for bilateral stones. On multivariate analysis, only TSV was an independent predictor of symptomatic events (HR, 1.35 per quartile; P = .01). This risk of events with TSV was also independent of demographics, urine chemistries, and stone composition. Among the 53 patients with interim events between CT scans, a rapid increase in TSV between CT scans (>570 mm(3) per year) predicted subsequent events (HR, 2.8; P = .05). CONCLUSION: Automated TSV is more predictive of symptomatic events than manual methods for quantifying stone burden on CT scan.

Nephron hypertrophy and glomerulosclerosis and their association with kidney function and risk factors among living kidney donors.

BACKGROUND AND OBJECTIVES: The relationship of kidney function and CKD risk factors to structural changes in the renal parenchyma of normal adults is unclear. This study assessed whether nephron hypertrophy and nephrosclerosis had similar or different associations with kidney function and risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1999 to 2009, 1395 living kidney donors had a core needle biopsy of their donated kidney during transplant surgery. The mean nonsclerotic glomerular volume and glomerular density (globally sclerotic and nonsclerotic) were estimated using the Weibel and Gomez stereologic methods. All tubules were counted in 1 cm(2) of cortex to determine a mean profile tubular area. Nephron hypertrophy was identified by larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density. Nephrosclerosis was identified by higher globally sclerotic glomerular density. RESULTS: The mean (± SD) age was 44 ± 12 years, 24-hour urine albumin excretion was 5 ± 7 mg, measured GFR was 103 ± 17 ml/min per 1.73 m(2), uric acid was 5.2 ± 1.4 mg/dl, and body mass index was 28 ± 5 kg/m(2). Of the study participants, 43% were men, 11% had hypertension, and 52% had a family history of ESRD. Larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density were correlated. Male sex, higher 24-hour urine albumin excretion, family history of ESRD, and higher body mass index were independently associated with each of these measures of nephron hypertrophy. Higher uric acid, higher GFR, and older age were also independently associated with some of these measures of nephron hypertrophy. Hypertension was not independently associated with measures of nephron hypertrophy. However, hypertension and older age were independently associated with higher globally sclerotic glomerular density. CONCLUSIONS: Nephron hypertrophy and nephrosclerosis are structural characteristics in normal adults that relate differently to clinical characteristics and may reflect kidney function and risk factors via separate but inter-related pathways.