Glomerular filtration rate, urine production, and fractional clearance of electrolytes in acute kidney injury in dogs and their association with survival.

BACKGROUND Acute kidney injury (AKI) is common in dogs. Few studies have assessed sequential changes in indices of kidney function in dogs with naturally occurring AKI. OBJECTIVE To document sequential changes of conventional indices of renal function, to better define the course of AKI, and to identify a candidate marker for recovery. ANIMALS Ten dogs with AKI. METHODS Dogs were prospectively enrolled and divided into surviving and nonsurviving dogs. Urine production was measured with a closed system for 7 days. One and 24-hour urinary clearances were performed daily to estimate solute excretion and glomerular filtration rate (GFR). Solute excretion was calculated as an excretion ratio (ER) and fractional clearance (FC) based on both the 1- and 24-hour urine collections. RESULTS Four dogs survived and 6 died. At presentation, GFR was not significantly different between the outcome groups, but significantly (P = .03) increased over time in the surviving, but not in the nonsurviving dogs. Fractional clearance of Na decreased significantly over time (20.2-9.4%, P < .0001) in the surviving, but not in the nonsurviving dogs. The ER and FC of solutes were highly correlated (r, 0.70-0.95). CONCLUSION AND CLINICAL IMPACT Excretion ratio might be used in the clinical setting as a surrogate marker to follow trends in solute excretion. Increased GFR, urine production, and decreased FC of Na were markers of renal recovery. The FC of Na is a simple, noninvasive, and cost-effective method that can be used to evaluate recovery of renal function.

Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. METHODS We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts > 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD. RESULTS Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white). CONCLUSIONS We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts > 500 cells/μL.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Determinants of renal tissue oxygenation as measured with BOLD-MRI in chronic kidney disease and hypertension in humans.

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Acute kidney injury in three dogs after ingestion of a descaling agent containing maleic acid

Maleic acid (MA) is a common component of descaling products and is widely used in daily life. Accidental ingestion in relevant amounts does not play a major role in human beings; however, it seems to be highly toxic for dogs. It has been commonly used experimentally to induce Fanconi syndrome in dogs or small rodents. Two dogs were presented for acute kidney injury (AKI) after accidental ingestion of a descaling agent containing MA at an estimated amount of 70 mg/kg each. The third dog involved was euthanased by the referring veterinarian, and postmortem pathological analysis revealed severe acute tubular necrosis consistent with toxic nephropathy. The other dogs received symptomatic therapy for AKI including treatment with haemodialysis and showed complete normalisation of serum creatinine at a follow-up after five months. Renal damage can be very severe, but seems to be at least partially reversible and an attempt to treatment is warranted.

Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial

BACKGROUND Renal damage is more frequent with new-generation lithotripters. However, animal studies suggest that voltage ramping minimizes the risk of complications following extracorporeal shock wave lithotripsy (SWL). In the clinical setting, the optimal voltage strategy remains unclear. OBJECTIVE To evaluate whether stepwise voltage ramping can protect the kidney from damage during SWL. DESIGN, SETTING, AND PARTICIPANTS A total of 418 patients with solitary or multiple unilateral kidney stones were randomized to receive SWL using a Modulith SLX-F2 lithotripter with either stepwise voltage ramping (n=213) or a fixed maximal voltage (n=205). INTERVENTION SWL. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was sonographic evidence of renal hematomas. Secondary outcomes included levels of urinary markers of renal damage, stone disintegration, stone-free rate, and rates of secondary interventions within 3 mo of SWL. Descriptive statistics were used to compare clinical outcomes between the two groups. A logistic regression model was generated to assess predictors of hematomas. RESULTS AND LIMITATIONS Significantly fewer hematomas occurred in the ramping group(12/213, 5.6%) than in the fixed group (27/205, 13%; p=0.008). There was some evidence that the fixed group had higher urinary β2-microglobulin levels after SWL compared to the ramping group (p=0.06). Urinary microalbumin levels, stone disintegration, stone-free rate, and rates of secondary interventions did not significantly differ between the groups. The logistic regression model showed a significantly higher risk of renal hematomas in older patients (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05; p=0.04). Stepwise voltage ramping was associated with a lower risk of hematomas (OR 0.39, 95% CI 0.19-0.80; p=0.01). The study was limited by the use of ultrasound to detect hematomas. CONCLUSIONS In this prospective randomized study, stepwise voltage ramping during SWL was associated with a lower risk of renal damage compared to a fixed maximal voltage without compromising treatment effectiveness. PATIENT SUMMARY Lithotripsy is a noninvasive technique for urinary stone disintegration using ultrasonic energy. In this study, two voltage strategies are compared. The results show that a progressive increase in voltage during lithotripsy decreases the risk of renal hematomas while maintaining excellent outcomes. TRIAL REGISTRATION ISRCTN95762080.

Proliferative kidney disease in brown trout – infection level, pathology and mortality under field conditions

Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild brown trout caught by electrofishing near the cage location were examined in parallel. The incidence of PKD in cage-exposed animals (69%) was not significantly different to the disease prevalence of wild fish (82 and 80% in the upstream and downstream locations, respectively). The mortality in cageexposed animals, however, was as low as 15%. At the termination of the exposure experiment, surviving fish showed histological lesions typical for PKD regression, suggesting that many YOY brown trout survive the initial infection. Our results at the River Wutach suggest that PKD in brown trout does not always result in high mortality under natural conditions.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still TOL. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.

Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. METHODS Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. RESULTS Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). CONCLUSION The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

[Transition in kidney transplantation]

Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

Diffusion tensor imaging of the human kidney: Does image registration permit scanning without respiratory triggering?

PURPOSE To investigate if image registration of diffusion tensor imaging (DTI) allows omitting respiratory triggering for both transplanted and native kidneys MATERIALS AND METHODS: Nine kidney transplant recipients and eight healthy volunteers underwent renal DTI on a 3T scanner with and without respiratory triggering. DTI images were registered using a multimodal nonrigid registration algorithm. Apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA) were determined. Relative root mean square errors (RMSE) of the fitting and the standard deviations of the derived parameters within the regions of interest (SDROI ) were evaluated as quality criteria. RESULTS Registration significantly reduced RMSE in all DTI-derived parameters of triggered and nontriggered measurements in cortex and medulla of both transplanted and native kidneys (P < 0.05 for all). In addition, SDROI values were lower with registration for all 16 parameters in transplanted kidneys (14 of 16 SDROI values were significantly reduced, P < 0.04) and for 15 of 16 parameters in native kidneys (9 of 16 SDROI values were significantly reduced, P < 0.05). Comparing triggered versus nontriggered DTI in transplanted kidneys revealed no significant difference for RMSE (P > 0.14) and for SDROI (P > 0.13) of all parameters. In contrast, in native kidneys relative RMSE from triggered scans were significantly lower than those from nontriggered scans (P < 0.02), while SDROI was slightly higher in triggered compared to nontriggered measurements in 15 out of 16 comparisons (significantly for two, P < 0.05). CONCLUSION Registration improves the quality of DTI in native and transplanted kidneys. Diffusion parameters in renal allografts can be measured without respiratory triggering. In native kidneys, respiratory triggering appears advantageous. J. Magn. Reson. Imaging 2016.

Racial Disparities in Access to and Outcomes of Kidney Transplantation in Children, Adolescents, and Young Adults: Results From the ESPN/ERA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) Registry.

BACKGROUND Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged ≤19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR Racial background. OUTCOMES & MEASUREMENTS Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups.