Background Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern ...associated with these structural findings is unclear. Study Design Cross-sectional (clinical-pathologic correlation). Setting & Participants Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. Predictors Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Outcomes Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Results Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Limitations Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Conclusions Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors.
Abstract Background Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for ...structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. Objectives This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. Methods We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Results Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio HR: 1.48; confidence interval CI: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). Conclusions SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.
Background Accurate assessment of kidney function is important for the management of solid-organ transplant recipients. In other clinical populations, glomerular filtration rate (GFR) most commonly ...is estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine or the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. The accuracy of these equations compared with other GFR estimating equations in transplant recipients has not been carefully studied. Study Design Diagnostic test study. Setting & Participants Solid-organ transplant recipients longer than 6 months posttransplantation from 5 clinical populations (N = 3,622, including recipients of kidney 53%, liver 35%, and other or multiple organs 12%). Index Test Estimated GFR (eGFR) using creatinine-based GFR estimating equations identified from a systematic review of the literature. Performance of the CKD-EPI creatinine and the MDRD Study equations was compared with alternative equations. Reference Test Measured GFR (mGFR) from urinary clearance of iothalamate or plasma clearance of iohexol. Measurements Error (difference between mGFR and eGFR) expressed as P30 (proportion of absolute percent error < 30%) and mean absolute error. Results We identified 26 GFR estimating equations. Mean mGFR was 55.1 ± 22.7 (SD) mL/min/1.73 m2 . P30 and mean absolute error for the CKD-EPI and the MDRD Study equations were 78.9% (99.6% CI, 76.9%-80.8%) for both and 10.6 (99.6% CI, 10.1-11.1) versus 11.0 (99.6% CI, 10.5-11.5) mL/min/1.73 m2 , respectively; these equations were more accurate than any of the alternative equations ( P < 0.001 for all pairwise comparisons for both measures). They performed better than or as well as the alternative equations in most subgroups defined by demographic and clinical characteristics, including type of transplanted organ. Limitations Study population included few nonwhites and people with solid-organ transplants other than liver and kidneys. Conclusions The CKD-EPI creatinine and the MDRD Study equations perform better than the alternative creatinine-based estimating equations in solid-organ transplant recipients. They can be used for clinical management.
Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what ...extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss.
We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models.
Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF.
These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes-many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.
Background Recent policy clarifications by the Centers for Medicare & Medicaid Services have changed access to outpatient dialysis care at end-stage renal disease (ESRD) facilities for individuals ...with acute kidney injury in the United States. Tools to predict “ESRD” and “acute” status in terms of kidney function recovery among patients who previously initiated dialysis therapy in the hospital could help inform patient management decisions. Study Design Historical cohort study. Setting & Participants Incident hemodialysis patients in the Mayo Clinic Health System who initiated in-hospital renal replacement therapy (RRT) and continued outpatient dialysis following hospital dismissal (2006 through 2009). Predictor Baseline estimated glomerular filtration rate (eGFR), acute tubular necrosis from sepsis or surgery, heart failure, intensive care unit, and dialysis access. Outcomes Kidney function recovery defined as sufficient kidney function for outpatient hemodialysis therapy discontinuation. Results Cohort consisted of 281 patients with a mean age of 64 years, 63% men, 45% with heart failure, and baseline eGFR ≥ 30 mL/min/1.73 m2 in 46%. During a median of 8 months, 52 (19%) recovered, most (94%) within 6 months. Higher baseline eGFR (HR per 10–mL/min/1.73 m2 increase eGFR, 1.27; 95% CI, 1.16-1.39; P < 0.001), acute tubular necrosis from sepsis or surgery (HR, 3.34; 95% CI, 1.83-6.24; P < 0.001), and heart failure (HR, 0.40; 95% CI, 0.19-0.78, P = 0.007) were independent predictors of recovery within 6 months, whereas first RRT in the intensive care unit and catheter dialysis access were not. There was a positive interaction between absence of heart failure and eGFR ≥ 30 mL/min/1.73 m2 for predicting kidney function recovery ( P < 0.001). Limitations Sample size. Conclusions Kidney function recovery in the outpatient hemodialysis unit following in-hospital RRT initiation is not rare. As expected, higher baseline eGFR is an important determinant of recovery. However, patients with heart failure are less likely to recover even with a higher baseline eGFR. Consideration of these factors at hospital discharge informs decisions on ESRD status designation and long-term hemodialysis care.
Background Although an arteriovenous fistula (AVF) is the hemodialysis access of choice, its prevalence continues to be lower than recommended in the United States. We assessed the association ...between past peripherally inserted central catheters (PICCs) and lack of functioning AVFs. Study Design Case-control study. Participants & Setting Prevalent hemodialysis population in 7 Mayo Clinic outpatient hemodialysis units. Cases were without functioning AVFs and controls were with functioning AVFs on January 31, 2011. Predictors History of PICCs. Outcomes Lack of functioning AVFs. Results On January 31, 2011, a total of 425 patients were receiving maintenance hemodialysis, of whom 282 were included in this study. Of these, 120 (42.5%; cases) were dialyzing through a tunneled dialysis catheter or synthetic arteriovenous graft and 162 (57.5%; controls) had a functioning AVF. PICC use was evaluated in both groups and identified in 30% of hemodialysis patients, with 54% of these placed after dialysis therapy initiation. Cases were more likely to be women (52.5% vs 33.3% in the control group; P = 0.001), with smaller mean vein (4.9 vs 5.8 mm; P < 0.001) and artery diameters (4.6 vs 4.9 mm; P = 0.01) than controls. A PICC was identified in 53 (44.2%) cases, but only 32 (19.7%) controls ( P < 0.001). We found a strong and independent association between PICC use and lack of a functioning AVF (OR, 3.2; 95% CI, 1.9-5.5; P < 0.001). This association persisted after adjustment for confounders, including upper-extremity vein and artery diameters, sex, and history of central venous catheter (OR, 2.8; 95% CI, 1.5-5.5; P = 0.002). Limitations Retrospective study, participants mostly white. Conclusion PICCs are commonly placed in patients with end-stage renal disease and are a strong independent risk factor for lack of functioning AVFs.
To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population.
Medical records were manually ...reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions.
There were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones (P<.001). Recurrence was similar across different proportions of calcium oxalate and hydroxyapatite (P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate (P for trend=.007).
Calcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.
Background The aim of the study was to determine whether a vancomycin dosing algorithm based on estimated glomerular filtration rate from creatinine and cystatin C levels (eGFRcr-cys ) improves ...target trough concentration achievement compared to an algorithm based on estimated creatinine clearance (eCLcr ) in critically ill patients. Study Design This prospective quality improvement project evaluated intensive care unit (ICU) patients started on intravenous vancomycin using one of 2 different strategies. Dosing regimens were selected and implemented after an individualized goal trough range was established (10-15 or 15-20 mg/L). Steady-state goal trough achievement was compared between treatment arms with and without adjustment for potential confounders. Setting & Participants 3 medical and surgical ICUs at a single tertiary medical center. Quality Improvement Plan During January 2012 to October 2013, vancomycin was dosed according to eCLcr using the Cockcroft-Gault formula (control arm). During December 2013 to May 2015, a multidisciplinary quality improvement team implemented a novel vancomycin dosing algorithm according to eGFRcr-cys using the CKD-EPI equation (intervention arm). Outcome Steady-state initial goal vancomycin trough concentration achievement. Measurements & Results More patients in the intervention arm (67 of 135 50%) achieved therapeutic trough vancomycin levels than in the control arm (74 of 264 28%; OR, 2.53; 95% CI, 1.65-3.90; P < 0.001). Improved trough achievement was maintained even after adjustment for age, sex, APACHE (Acute Physiology and Chronic Health Evaluation) III score, fluid balance, baseline CLcr , surgical admission diagnosis, presence of sepsis, and goal trough concentration range (adjusted OR, 2.79; 95% CI, 1.76-4.44; P < 0.001). Clinical outcomes were similar between groups. Limitations Nonrandomized, incomplete algorithm compliance. Conclusions A vancomycin dosing nomogram based on eGFRcr-cys significantly improved goal trough achievement compared to eCLcr among ICU patients with stable kidney function. Further studies are warranted to characterize the relationship between use of cystatin C−guided dosing and clinical outcomes.
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 (rs =−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.
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.
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