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.
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.
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).
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.
Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and ...HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.
Background The presence of a few renal cysts is considered of little relevance in healthy adults, although acquired renal cystic disease occurs in advanced kidney failure. The objective of this study ...was to detail renal cystic and solid lesions and identify any association with clinical characteristics. Study Design Clinical-pathologic correlation. Setting & Participants Potential kidney donors undergoing a standardized evaluation at the Mayo Clinic in 2000-2008. Predictors Age, kidney function, and chronic kidney disease risk factors. Measurements Renal cystic and solid lesions by contrast-enhanced computed tomographic images. Outcomes Cyst number, diameter, and location. Results After excluding 8 with cystic disease, 7 of whom had autosomal dominant polycystic kidney disease, there were 1,948 potential kidney donors (42% men; mean age, 43 years). A cortical, medullary, or parapelvic cyst ≥5 mm was present in 12%, 14%, or 2.8%. For ages 19-49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. For ages 50-75 years, 63%, 43%, 22%, and 7.8% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. The 97.5th percentile for number of cortical and medullary cysts ≥5 mm increased with age (10 for men and 4 for women in the 60- to 69-year group). After age and sex adjustment, cortical and medullary cysts ≥5 mm were associated with higher 24-hour urine albumin excretion, as well as increased body surface area, hypertension, and higher glomerular filtration rate in some analyses. Angiomyolipomas, hyperdense cysts, and enhancing masses or cysts with concerning features for malignancy occurred in 2.2%, 1.2%, and 0.6% and were associated with older age ( P ≤ 0.05 for each). Limitations Persons with known chronic kidney disease were excluded. Conclusions Renal cysts are common, particularly in older men, and may be a marker of early kidney injury because they associate with albuminuria, hypertension, and hyperfiltration.
Background
The objective of this systematic review and meta-analysis were to evaluate the effectiveness of high fluid intake for the prevention of incident and recurrent kidney stones, as well as its ...adherence and safety.
Methods
A literature search was performed encompassing 1980 through July 2014. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risk of kidney stone events in patients with high vs inadequate fluid intake were included. Pooled risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method.
Results
Nine studies 2 randomized controlled trials (RCTs) with 269 patients; 7 observational studies with 273,685 individuals were included in the meta-analysis. Pooled RRs of kidney stones in individuals with high-fluid intake were 0.40 (95 % CI 0.20–0.79) and 0.49 (0.34–0.71) in RCTs and observational studies, respectively. High fluid intake was significantly associated with reduced risk of recurrent kidney stones: RRs 0.40 (95 % CI 0.20–0.79) and 0.20 (0.09–0.44) in RCTs and observational studies, respectively. Adherence and safety data on high fluid intake treatment were limited; 1 RCT reported no withdrawals due to adverse events.
Conclusion
This analysis demonstrated a significantly reduced risk of incident kidney stones among individuals with high fluid consumption. High fluid consumption also reduced the risk of recurrent kidney stones. Furthermore, the magnitude of risk reduction was high. Although increased water intake appears to be safe, future studies on its safety in patients with high risk of volume overload or hyponatremia may be indicated.
Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has ...focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement.
The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion.
Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.
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