Iohexol plasma clearance measurement protocol standardization for adults: a consensus paper of the European Kidney Function Consortium.

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation.

A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13%, respectively), or underwent pre-emptive KTx (4%; 3%, respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland.

OBJECTIVES: Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model. METHODS: We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008-16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0-29, 30-44, 45-59, 60-74, 75-89, 90-104 and >104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality. RESULTS: We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18-106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75-89 mL/min/1.73 m2 without proteinuria. For persons aged >65 years, the lowest risk was observed for eGFR of 60-74 mL/min/1.73 m2 without proteinuria. eGFR of 45-59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104 mL/min/1.73 m2 associated with increased mortality. CONCLUSIONS: These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortality.

Sequence variants associating with urinary biomarkers.

Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.5 million sequence variants for association with urinary biomarkers in a set of 150 274 Icelanders with urine dipstick measurements. We detected 20 association signals, of which 14 are novel, associating with at least one of five clinical entities defined by the urine dipstick: glucosuria, ketonuria, proteinuria, hematuria and urine pH. These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes. Two variants associating with proteinuria are in LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal tubule protein uptake. One of the hematuria-associated variants is a rare, previously unreported 2.5 kb exonic deletion in COL4A3. Of the four signals associated with urine pH, we note that the pH-increasing alleles of two variants (POU2AF1, WDR72) associate significantly with increased risk of kidney stones. Our results reveal that genetic factors affect variability in urinary biomarkers, in both a disease dependent and independent context.

GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts.

BACKGROUND: Population mean GFR is lower in older age, but it is unknown whether healthy aging is associated with preserved rather than lower GFR in some individuals. METHODS: We investigated the cross-sectional association between measured GFR, age, and health in persons aged 50-97 years in the general population through a meta-analysis of iohexol clearance measurements in three large European population-based cohorts. We defined a healthy person as having no major chronic disease or risk factors for CKD and all others as unhealthy. We used a generalized additive model to study GFR distribution by age according to health status. RESULTS: There were 935 (22%) GFR measurements in persons who were healthy and 3274 (78%) in persons who were unhealthy. The mean GFR was lower in older age by -0.72 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], -0.96 to -0.48) for men who were healthy versus -1.03 ml/min per 1.73 m2 per year (95% CI, -1.25 to -0.80) for men who were unhealthy, and by -0.92 ml/min per 1.73 m2 per year (95% CI, -1.14 to -0.70) for women who were healthy versus -1.22 ml/min per 1.73 m2 per year (95% CI, -1.43 to -1.02) for women who were unhealthy. For healthy and unhealthy people of both sexes, both the 97.5th and 2.5th GFR percentiles exhibited a negative linear association with age. CONCLUSIONS: Healthy aging is associated with a higher mean GFR compared with unhealthy aging. However, both the mean and 97.5 percentiles of the GFR distribution are lower in older persons who are healthy than in middle-aged persons who are healthy. This suggests that healthy aging is not associated with preserved GFR in old age.

The prevalence of chronic kidney disease in Iceland according to KDIGO criteria and age-adapted estimated glomerular filtration rate thresholds.

Most epidemiological studies on chronic kidney disease (CKD) are based solely on estimated glomerular filtration rate (eGFR). Few studies have included proteinuria, while the chronicity criterion is usually omitted. To explore this, we examined the prevalence of CKD stages 1-5 in Iceland based on multiple markers of kidney damage. All serum creatinine values, urine protein measurements and diagnostic codes for kidney diseases and comorbid conditions for people aged 18 years and older were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline using diagnoses indicative of a chronic kidney disease, proteinuria and/or an eGFR under 60 mL/min/1.73 m2 for over three months. Mean annual age-standardized prevalence of CKD stages 1-5 was calculated based on the KDIGO criteria and age-adapted eGFR thresholds from 2,120,147 creatinine values for 218,437 individuals, 306,531 proteinuria measurements for 86,364 individuals and 6973 individuals carrying a kidney disease diagnosis. Median age was 63 years (range, 18-106) and 47% were male. The mean annual age standardized CKD prevalence was 5.13% for men and 6.75% for women using the KDIGO criteria but by age-adapted eGFR cut-offs, the prevalence was 3.27% for men and 4.01% for women. Thus, our nationwide study, defining CKD in Iceland with strict adherence to the KDIGO criteria, demonstrates a lower prevalence of CKD than anticipated from most previous studies.

CKD: A Call for an Age-Adapted Definition.

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay. METHODS: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (rs). RESULTS: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (rs = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls. CONCLUSIONS: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.

Postoperative Acute Kidney Injury: Focus on Renal Recovery Definitions, Kidney Disease Progression and Survival.

BACKGROUND: The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD). METHODS: This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 × baseline, (ii) 1.1-1.25 × baseline, (iii) 1.25-1.5 × baseline, and (iv) > 1.5 × baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups. RESULTS: In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 × baseline (hazard ratio [HR] 1.50; 95% CI 1.29-1.75) and if renal recovery was limited to a fall in SCr to 1.25-1.5 × baseline (HR 1.32; 95% CI 1.12-1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 × baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 × baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001). CONCLUSIONS: These findings should be considered when a consensus definition of renal recovery after AKI is established.

Long-term renal outcomes of APRT deficiency presenting in childhood.

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary purine metabolism disorder that causes kidney stones and chronic kidney disease (CKD). The purpose of this study was to examine the course of APRT deficiency in patients who presented in childhood. METHODS: The disease course of 21 (35%) patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, who presented with manifestations of APRT deficiency and/or were diagnosed with the disorder before the age of 18 years, was studied. The effect of pharmacotherapy on renal manifestations and outcomes was thoroughly assessed. RESULTS: Fourteen children were placed on allopurinol, 100 (25-200) mg/day, at the age of 2.6 (0.6-16.5) years. Six of these patients had experienced kidney stone events and three had developed acute kidney injury (AKI) prior to allopurinol treatment. During 18.9 (1.7-31.5) years of pharmacotherapy, stones occurred in two patients and AKI in three. Six adult patients started allopurinol treatment, 200 (100-300) mg/day, at age 29.8 (20.5-42.4) years. Five of these patients had experienced 28 stone episodes and AKI had occurred in two. Stone recurrence occurred in four patients and AKI in two during 11.2 (4.2-19.6) years of allopurinol therapy. Lack of adherence and insufficient dosing contributed to stone recurrence and AKI during pharmacotherapy. At latest follow-up, estimated glomerular filtration rate (eGFR) was 114 (70-163) and 62 (10-103) mL/min/1.73 m2 in those who initiated treatment as children and adults, respectively. All three patients with CKD stages 3-5 at the last follow-up were adults when pharmacotherapy was initiated. CONCLUSION: Timely diagnosis and treatment of APRT deficiency decreases renal complications and preserves kidney function.

Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

Background: Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys). Methods: A total of 805 individuals, 74-93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2. Results: All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations. Conclusion: None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations.

Incidence of kidney stone disease in Icelandic children and adolescents from 1985 to 2013: results of a nationwide study.

BACKGROUND: An increase in the incidence of kidney stone disease has been reported for all age groups worldwide. To examine this trend, we conducted a nationwide study of the epidemiology of kidney stones in Icelandic children and adolescents over a 30-year period. METHODS: Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases and radiologic and surgical procedure codes indicative of kidney stones in patients aged < 18 years, followed by a thorough medical record review. Age-adjusted incidence was calculated for the time intervals 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010-2013. Time trends in stone incidence were assessed by Poisson regression. The prevalence of stone disease for the years 1999-2013 was also determined. RESULTS: Almost all the 190 patients (97%) that we identified had symptomatic stones, and acute flank or abdominal pain and hematuria were the most common presenting features. The total annual incidence of kidney stones increased from 3.7/100,000 in the first 5-year interval to 11.0/100,000 during the years 1995-2004 (p < 0.001) and decreased thereafter to 8.7/100,000 in 2010-2013 (p = 0.63). The incidence rise was highest in girls aged 13-17 years, in whom it rose from 9.8/100,000 in 1985-1989 to 39.2/100,000 in 2010-2013 (p < 0.001), resulting in an overall female predominance in this age group. The mean annual prevalence of stone disease in 1999-2013 was 48/100,000 for boys and 52/100,000 for girls. CONCLUSION: We found a significant increase in the incidence of childhood kidney stone disease, driven by a dramatic increase of stone frequency in teenage females which is poorly understood and warrants further study.

Reduced anticoagulation variability in patients on warfarin monitored with Fiix-prothrombin time associates with reduced thromboembolism: The Fiix-trial.

Fiix-prothrombin time (Fiix-PT) differs from traditional PT in being affected by reduced factor (F) II or FX only. In the randomized controlled Fiix-trial, patients on warfarin monitored with Fiix-PT (Fiix-warfarin patients) had fewer thromboembolisms (TE), similar major bleeding (MB) and more stable anticoagulation than patients monitored with PT (PT-warfarin patients). In the current Fiix-trial report we analyzed how reduced anticoagulation variability during Fiix-PT monitoring was reflected in patients with TE or bleeding. Data from 1143 randomized patients was used. We analyzed the groups for anticoagulation intensity (time within target range; TTR), international normalized ratio (INR) variability (variance growth rate B1; VGR) and dose adjustment frequency. We assessed how these parameters associated with clinically relevant vascular events (CRVE), ie TE or MB or clinically relevant non-MB. TTR was highest in Fiix-warfarin patients without CRVE (median 82%;IQR 72-91) and lowest in PT-warfarin patients with TE (62%;56-81). VGR was lowest in Fiix-warfarin patients without CRVE (median VGR B1 0.17; 95% CI 0.08-0.38) and with TE (0.20;0.07-0.26) and highest in PT-warfarin patients with TE (0.50;0.27-0.90) or MB (0.59;0.07-1.36). The mean annual dose adjustment frequency was lowest in Fiix-warfarin patients with TE (mean 5.4;95% CI 3.9-7.3) and without CRVE (mean 6.0; 5.8-6.2) and highest in PT-warfarin patients with TE (14.2;12.2-16.3). Frequent dose changes predicted MB in both study arms. Compared to patients monitored with PT, high anticoagulation stability in Fiix-warfarin patients coincided with their low TE rate. Those with bleeding had high variability irrespective of monitoring method. Thus, although further improvements are needed to reduce bleeding, stabilization of anticoagulation by Fiix-PT monitoring associates with reduced TE.

Rare mutations associating with serum creatinine and chronic kidney disease.

Chronic kidney disease (CKD) is a complex disorder with a strong genetic component. A number of common sequence variants have been found to associate with serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and/or CKD. We imputed 24 million single-nucleotide polymorphisms and insertions/deletions identified by whole-genome sequencing of 2230 Icelanders into 81 656 chip-typed individuals and 112 630 relatives of genotyped individuals over the age of 18 with SCr measurements. The large set of sequenced individuals allowed accurate imputation of variants to a minor allele frequency (MAF) of 0.1%. We tested the imputed variants for association with SCr. In addition to replicating established loci, we discovered missense and loss-of-function variants associating with SCr in three solute carriers (SLC6A19, SLC25A45 and SLC47A1) and two E3 ubiquitin ligases (RNF186 and RNF128). All the variants are within coding sequences and all but one are rare (MAF <2%) with SCr effects between 0.085 and 0.129 standard deviations. These rare variants have a larger effect on SCr than previously reported common variants, explaining 0.5% of the variability of SCr in Icelanders in addition to the 1% already accounted for. We tested the five variants associating with SCr for association with CKD in an Icelandic sample of 15 594 cases and 291 428 controls. Three of the variants also associated with CKD. These variants may either affect kidney function or creatinine synthesis and excretion. Of note were four mutations in SLC6A19 that associate with reduced SCr, three of which have been shown to cause Hartnup disease.

Kidney Disease in Adenine Phosphoribosyltransferase Deficiency.

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a purine metabolism disorder causing kidney stones and chronic kidney disease (CKD). The course of nephrolithiasis and CKD has not been well characterized. The objective of this study was to examine long-term kidney outcomes in patients with APRT deficiency. STUDY DESIGN: An observational cohort study. SETTING & PARTICIPANTS: All patients enrolled in the APRT Deficiency Registry of the Rare Kidney Stone Consortium. OUTCOMES: Kidney stones, acute kidney injury (AKI), stage of CKD, end-stage renal disease, estimated glomerular filtration rate (eGFR), and changes in eGFR. MEASUREMENTS: Serum creatinine and eGFR calculated using creatinine-based equations. RESULTS: Of 53 patients, 30 (57%) were females and median age at diagnosis was 37.0 (range, 0.6-67.9) years. Median duration of follow-up was 10.3 (range, 0.0-31.5) years. At diagnosis, kidney stones had developed in 29 (55%) patients and 20 (38%) had CKD stages 3 to 5, including 11 (21%) patients with stage 5. At latest follow-up, 33 (62%) patients had experienced kidney stones; 18 (34%), AKI; and 22 (42%), CKD stages 3 to 5. Of 14 (26%) patients with stage 5 CKD, 12 had initiated renal replacement therapy. Kidney stones recurred in 18 of 33 (55%) patients. The median eGFR slope was -0.38 (range, -21.99 to 1.42) mL/min/1.73m(2) per year in patients receiving treatment with an xanthine dehydrogenase inhibitor and -5.74 (range, -75.8 to -0.10) mL/min/1.73m(2) per year in those not treated prior to the development of stage 5 CKD (P=0.001). LIMITATIONS: Use of observational registry data. CONCLUSIONS: Progressive CKD and AKI episodes are major features of APRT deficiency, whereas nephrolithiasis is the most common presentation. Advanced CKD without a history of kidney stones is more prevalent than previously reported. Our data suggest that timely therapy may retard CKD progression.

Acute Kidney Injury After Abdominal Surgery: Incidence, Risk Factors, and Outcome.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after major surgical procedures. We examined the incidence, risk factors, and mortality of patients who sustained AKI after abdominal surgery in a large population-based cohort. METHODS: All patients who underwent open and laparoscopic abdominal surgery (excluding genitourinary and abdominal vascular procedures), between 2007 and 2014 at the University Hospital in Reykjavik were identified and their perioperative serum creatinine (SCr) measurements used to identify AKI after surgery employing the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Risk factors were evaluated using multivariate logistic regression analysis and 30-day mortality compared with a propensity score-matched control group. RESULTS: During the 8-year period, a total of 11,552 abdominal surgeries were performed on 10,022 patients. Both pre- and postoperative SCr measurements were available for 3902 (33.8%) of the surgical cases. Of these, 264 (6.8%) were complicated by AKI; 172 (4.4%), 49 (1.3%), and 43 (1.1%) were classified as KDIGO stages 1, 2 and 3, respectively. The overall incidence of AKI for patients with available SCr values was 67.7 (99% confidence interval [CI], 57.7-78.6) per 1000 surgeries. In logistic regression analysis, independent risk factors for AKI were female sex (odds ratio [OR] = 0.68; 99% CI, 0.47-0.98), hypertension (OR = 1.75; 99% CI, 1.10-2.74), preoperative chronic kidney disease (OR= 1.68; 99% CI, 1.12-2.50), ASA physical status classification of IV (OR = 9.48; 99% CI, 3.66-29.2) or V (OR = 21.4; 99% CI, 5.28-93.6), and reoperation (OR = 4.30; 99% CI, 2.36-7.70). Patients with AKI had greater 30-day mortality (18.2% vs 5.3%; P < 0.001) compared with propensity score-matched controls. CONCLUSIONS: AKI is an important complication of abdominal surgery. In addition to sex, hypertension, and chronic kidney disease, ASA physical status classification is an independent predictor of AKI. Individuals who develop AKI have substantially worse short-term outcomes, including higher 30-day mortality, even after correcting for multiple patient- and procedure-related risk factors.

Improved long-term survival and renal recovery after acute kidney injury in hospitalized patients: A 20 year experience.

AIM: Acute kidney injury (AKI) is a common complication of medical and surgical interventions in hospitalized patients and associates with high mortality. Our aim was to examine renal recovery and long-term survival and time trends in AKI survival. METHODS: Changes in serum creatinine (SCr) were used to define AKI in patients at Landspitali University Hospital in Iceland from 1993 to 2013. Renal recovery was defined as SCr < 1.5× baseline. RESULTS: Out of 25 274 individuals who had their highest measured SCr during hospitalization and an available baseline SCr, 10,419 (41%) had AKI during hospitalization (H-AKI), 19%, 11% and 12% with Stage 1, 2 and 3, respectively. The incidence of H-AKI increased from 18.6 (95% CI, 14.7-22.5) to 29.9 (95% CI, 26.7-33.1) per 1000 admissions/year over the study period. Survival after H-AKI was 61% at 90-days and 51% at one year. Comparing H-AKI patients to propensity score matched individuals the hazard ratio for death was 1.49 (1.36-1.62), 2.17 (1.95-2.41) and 2.95 (2.65-3.29) for Stage 1, 2 and 3, respectively. One-year survival of H-AKI patients improved from 47% in 1993-1997 to 57% in 2008-2013 and the adjusted hazard ratio for mortality improved, compared to the first 5-year period, 0.85 (0.81-0.89), 0.67 (0.64-0.71), and 0.57 (0.53-0.60) for each subsequent 5-year interval. Recovery of renal function was achieved in 88%, 58% and 44% of patients in Stages 1, 2 and 3, respectively, improving with time. CONCLUSIONS: Acute kidney injury is an independent predictor of long-term mortality in hospitalized patients but there has been a marked improvement in survival and renal recovery over the past two decades.

Comparing GFR Estimating Equations Using Cystatin C and Creatinine in Elderly Individuals.

Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone. However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy. We first compared the Japanese, BIS, and CAPA equations with the CKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations. Mean (SD) age was 80.3 (4.0) years. Median (25th, 75th) mGFR was 64 (52, 73) ml/min per 1.73 m(2), and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisons with the other equations, CKD-EPI equations performed better in 9, similar in 13, and worse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys.

Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort.

BACKGROUND: Chronic kidney disease (CKD) is common in the elderly, but the cause is often not identifiable. Some posit that age-related reductions in glomerular filtration rate (GFR) and increases in albuminuria are normal, whereas others suggest that they are a consequence of vascular disease. STUDY DESIGN: Cross-sectional analysis of a substudy of a prospective cohort. SETTING & PARTICIPANTS: AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study. PREDICTOR: Exposure to higher blood pressure in midlife. OUTCOMES & MEASUREMENTS: Measured GFR using plasma clearance of iohexol and urine albumin-creatinine ratio. RESULTS: GFR was measured in 805 participants with mean age in midlife and late life of 51.0±5.8 and 80.8±4.0 (SD) years, respectively. Mean measured GFR was 62.4±16.5 mL/min/1.73 m(2) and median albuminuria was 8.0 (IQR, 5.4-16.5) mg/g. Higher midlife systolic and diastolic blood pressures were associated with lower later-life GFRs. Associations persisted after adjustment. Higher midlife systolic and diastolic blood pressures were also associated with higher albumin-creatinine ratios, and associations remained significant even after adjustment. LIMITATIONS: This is a study of survivors, and people who agreed to participate in this study were healthier than those who refused. Blood pressure may encompass effects of the other risk factors. Results may not be generalizable to populations of other races. We were not able to adjust for measured GFR or albuminuria at the midlife visit. CONCLUSIONS: Factors other than advanced age may account for the high prevalence of CKD in the elderly. Midlife factors are potential contributing factors to late-life kidney disease. Further studies are needed to identify and treat midlife modifiable factors to prevent the development of CKD.

Impact of nephrolithiasis on kidney function.

BACKGROUND: Kidney stone disease has been associated with reduced kidney function and chronic kidney disease (CKD). The objective of the study was to examine kidney function, body mass index (BMI) and the prevalence of cardiovascular disease, hypertension and diabetes in recurrent kidney stone formers. METHODS: A cross-sectional, case-control study comparing measures of kidney function, BMI and comorbid conditions was conducted in 195 kidney stone patients aged 18 to 70 years with recurrent clinical stone events and 390 age- and gender-matched controls. Wilcoxon-Mann-Whitney, chi-square tests and analysis of covariance were used to compare serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) between the groups. RESULTS: The median age of stone formers was 51 (range, 19-70) years and 108 (55 %) were males. Seventy patients (36 %) had experienced 2-4 clinical stone events, 41 (21 %) 5-10 episodes and 84 (43 %) more than 10. The median SCr was 75 (41-140) µmol/L in the stone formers and 64 (34-168) µmol/L in the control group (p < 0.001). The mean eGFR was 87 ± 20 and 104 ± 22 mL/min/1.73 m(2) in the stone formers and controls, respectively (p < 0.001). After adjustment for body size and comorbid conditions, the difference in SCr and eGFR between cases and controls remained highly significant (p < 0.001). The prevalence of CKD was 9.3 % among stone formers compared with 1.3 % in the control group (P < 0.001). Hypertension and diabetes were significantly more prevalent among the cases that also had higher BMI than controls. CONCLUSIONS: Recurrent kidney stone formers have a significantly lower level of kidney function and a markedly higher prevalence of CKD than age- and gender-matched control subjects. The observed deleterious effect of kidney stones on kidney function appears to be independent of comorbid conditions.