Presence of Sarcopenia before Kidney Transplantation Is Associated with Poor Outcomes.

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with renal failure. It is crucial to select which patients may benefit from renal transplantation and which are at high risk for post-transplant complications. Sarcopenia is associated with poor outcome in various conditions, including in chronic kidney disease patients. The gold standard for measuring sarcopenia is computed tomography (CT) imaging to estimate muscle mass and quality since it is objective, reproducible, and reflects the overall health condition. The data regarding those measurements among kidney transplant recipients are limited, therefore we aimed to describe it in patients before kidney transplantation, assess the parameters associated with sarcopenia, and evaluate the clinical significance of those markers on outcomes following transplantation. METHODS: We retrospectively analyzed 183 kidney transplant recipients who had a CT scan 90 days prior to transplant. Sarcopenia was assessed by measuring the cross-sectional area (CSA) and mean muscle density of the psoas muscle at the third and fourth lumbar vertebrae levels and paravertebral muscles at the 12th thoracic vertebra level. RESULTS: There was a strong linear correlation between muscle size measured as CSA of the psoas muscle at the L3 and L4 vertebral body level and the CSA of the paravertebral muscles at the D12 vertebra level, and a moderate correlation to muscle density at those levels. Age was independently associated with risk of sarcopenia, defined as psoas CSA in the lowest tertile, with every year of age increasing the risk by 5%. CSA at the L3 level had a significant independent association with post kidney transplantation mortality, with an adjusted hazard ratio of 0.86 per cm2. There was a significantly longer hospitalization period postoperation in kidney recipients in the lower tertile of psoas CSA and density. CONCLUSIONS: Sarcopenia as measured by psoas CSA is associated with poor short- and long-term outcomes following kidney transplantation and should be included as part of the assessment of kidney transplantation candidates.

Nonalcoholic Fatty Liver Disease before Kidney Transplantation Correlates with New Onset Diabetes and Poor Metabolic Outcomes.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality after kidney transplantation. Metabolic syndrome is common in renal transplant recipients and is associated with increased CVD risk in those patients. Nonalcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of a multi-system disorder, including CVD and metabolic syndrome. The data about prevalence of NAFLD before kidney transplantation and its consequences following transplantation are scarce. METHODS: A retrospective study of metabolic parameters and sonographic evidence of NAFLD, and an analysis of its metabolic outcomes, was performed in 341 consecutive kidney transplant recipients. RESULTS: One-hundred twenty-four (36.4%) kidney recipients had NAFLD before transplantation. The risk of NAFLD before kidney transplantation was independently and significantly related to diabetes (OR = 1.8), male gender (OR = 1.4), older age (every year of age increased the risk by 4%), higher BMI (every increase of 1 kg/m2 increased the risk by 15%), and higher triglycerides level. Mean levels of liver enzymes were similar in patients with and without NAFLD. Recipients with NAFLD before transplantation had a higher prevalence of new onset diabetes, even after adjustment to covariables. In addition, they had a higher increase in liver enzymes, triglycerides, and FIB-4 score, as an indication of liver fibrosis, after transplantation. Furthermore, NAFLD pre-transplantation was independently associated with cardiovascular mortality (HR = 4.4) following kidney transplantation. CONCLUSIONS: Sonographic evidence of NAFLD before kidney transplantation is associated with significant metabolic outcomes including de novo diabetes and cardiovascular mortality following transplantation and should be included as part of the assessment of kidney transplant candidate.

Water avoidance and modification of exit-site care with stoma bag results in reduced exit-site infection rate in peritoneal dialysis patients.

AIM: Infection is one of the drawbacks associated with peritoneal dialysis (PD) and is related to significant morbidity. After we experienced an increase in exit-site infection (ESI) rate, mostly derived from environmental and water-derived organisms, we hypothesized that preventing exit-site exposure to water and narrowing local antibiotics range will reduce colonization and subsequent infection. MATERIALS AND METHODS: In this study, we aimed to estimate PD-related infections after exit-site policy change in a prospective study cohort of 27 participants compared to a control group of 58 participants. The modification of exit-site care consisted of applying a stoma bag during daily shower to prevent water exposure and conversion of local antibiotic from gentamycin to mupirocin. Primary outcome was catheter-related infection. Secondary outcomes were peritonitis rate and infection-related outcomes. RESULTS: The study group had a significantly lower ESI and ESI from environmental organisms' free probability. Rate of ESI from all causes was 0.054 ± 0.09 vs. 0.031 ± 0.09 episodes per patients' month for the control and study group, respectively (p = 0.049). Rate of environmental organism-related ESI was 0.047 ± 0.07 vs. 0.015 ± 0.08 episodes per patients' months for control and study group, respectively (p = 0.042). A higher risk of ESI from all organisms, and specifically from environmental organisms, was associated with being in the control group and a longer follow-up period. Rate of peritonitis was similar in both groups. CONCLUSION: The adjusted exit-site care policy significantly lowered ESI incidence. Avoidance of water exposure may have contributed to lessen bacterial colonization.

WoundClot® Hemostatic Gauze Reduces Bleeding Time after Arterial Venous Fistula Decannulation.

INTRODUCTION: Decannulation of the arteriovenous fistula (AVF) after each hemodialysis session requires a precise compression on the needle puncture site. The objective of our study was to evaluate the bleeding time (BT) needed to achieve hemostasis using WoundClot, an innovative hemostatic gauze, and to assess whether its long-term use can improve AVF preservation. METHODS: This is a prospective single center study. Initially, the time to hemostasis after AVF decannulation was compared between WoundClot and cotton gauze in 24 prevalent hemodialysis patients. Thereafter, the patients continued to use WoundClot for 12 months and were compared to a control group consisting of 25 patients using regular cotton gauze. Follow-up data included parameters of dialysis adequacy, AVF interventions, and thrombotic events. RESULTS: WoundClot use shortened significantly the time needed for hemostasis. Mean venous BT decreased by 3.99 (±4.6) min and mean arterial BT by 6.38 (±4.8) min when using WoundClot compared to cotton gauze (p < 0.001). At the end of the study, dialysis adequacy expressed by spKt/V was higher in the WoundClot group compared to control (1.73 vs. 1.53, respectively, p = 0.047). Although patients in WoundClot group had a higher baseline BT, arterial and venous pressures did not differ between the groups after a median follow up of 10.8 months. AVF thrombosis rate was similar between the groups. CONCLUSIONS: WoundClot hemostatic gauze significantly reduced the time required for hemostasis after AVF decannulation and may be associated with better AVF preservation. We suggest using WoundClot for arterial BT longer than 15 min and for venous BT longer than 12.5 min.

Acute kidney injury after transcatheter aortic valve implantation and mortality risk-long-term follow-up.

BACKGROUND: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up. METHODS: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis. RESULTS: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022). CONCLUSIONS: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.

Ultrapure Filter does not Confer Short-Term Benefits over Two Reverse Osmosis Systems in Chronic Hemodialysis Patients.

BACKGROUND: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients. OBJECTIVES: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF). METHODS: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group. RESULTS: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls. CONCLUSIONS: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.

Mineralocorticoid receptor blockade improves arginine transport and nitric oxide generation through modulation of cationic amino acid transporter-1 in endothelial cells.

Blockade of the mineralocorticoid receptor (MCR) has been shown to improve endothelial function far beyond blood pressure control. In the current studies we have looked at the effect of MCR antagonists on cationic amino acid transporter-1 (CAT-1), a major modulator of endothelial nitric oxide (NO) generation. Using radio-labeled arginine, {[3H] l-arginine} uptake was determined in human umbilical vein endothelial cells (HUVEC) following incubation with either spironolactone or eplerenone with or without silencing of MCR. Western blotting for CAT-1, PKCα and their phosphorylated forms were performed. NO generation was measured by using Griess reaction assay. Both Spironolactone and eplerenone significantly increased endothelial arginine transport, an effect which was further augmented by co-incubation with aldosterone, and blunted by either silencing of MCR or co-administration of amiloride. Following MCR blockade, we identified two bands for CAT-1. The addition of tunicamycin (an inhibitor of protein glycosylation) or MCR silencing resulted in disappearance of the extra band and prevented the increase in arginine transport. Only spironolactone decreased CAT-1 phosphorylation through inhibition of PKCα (CAT-1 inhibitor). Subsequently, incubation with either MCR antagonists significantly augmented NO2/NO3 levels (stable NO metabolites) and this was attenuated by silencing of MCR or tunicamycin. GO 6076 (PKCα inhibitor) intensified the increase of NO metabolites only in eplerenone treated cells. In conclusion spironolactone and eplerenone augment arginine transport and NO generation through modulation of CAT-1 in endothelial cells. Both MCR antagonists activate CAT-1 by inducing its glycosylation while only spironolactone inhibits PKCα.

Use of lung ultrasound to assess volume status and its association with physical examination in patients with chronic kidney disease.

Introduction: Defining the optimal hydration status in patients with chronic kidney disease (CKD) is challenging, and the quest for an objective accurate method continues. Lung ultrasound (LUS) is a well-validated technique to estimate volume status. Previous studies examining the relationship between LUS and physical examination demonstrated conflicting results. We aimed to evaluate the correlation between LUS results and physical examination for assessing volume status in patients with CKD, and to compare different LUS protocols. Methods: A prospective, single-center trial correlating physical examination findings to LUS results in different CKD groups, including non-dialysis and dialysis patients. Hemodialysis patients were tested twice, before and after dialysis, to compare results with ultrafiltration volume. Different LUS protocols were performed and compared, including 16-, 12-, and 8-zone measurements. Results: We recruited 175 participants. A strong positive correlation was demonstrated between 16- and 12-zone protocols [r = .91 (P < .001)] and between 12- and 8-zone protocols (r = .951, P < .001). Correlation was significant in various CKD groups. While blood pressure did not correlate with LUS score, there was a significant correlation between LUS and other components of the physical examination including lung crackles (OR = 1.15 (95%CI 1.096-1.22), P < .01), pleural effusion (OR = 1.15 (95%CI 1.09-2.13), P < .01) and peripheral edema (r = .24, P < .001). Ultrafiltration volume did not correlate significantly with change in LUS scores pre- and post-dialysis (r = .169, P = .065). Conclusion: Most components of physical examination findings correlated with extravascular lung water assessment on LUS in CKD patients. The use of a simplified pragmatic LUS protocol may facilitate LUS use in clinical practice.

Assessment of the Correlation Between Serum Phosphate Level and Muscle Strength as Measured by Handgrip Strength in Patients Treated With Hemodialysis.

Background: Sarcopenia, commonly observed in patients treated with hemodialysis, correlates with low serum phosphate levels. Although normophosphatemia is desired, dietary phosphate restriction is difficult to achieve and may result in undesirable protein restriction. Objective: We aimed to evaluate whether hyperphosphatemia is associated with higher muscle strength in patients receiving hemodialysis treatment. Design: A single-center prospective observational study. Setting: Ambulatory prevalent patients undergoing hemodialysis treatments in a dialysis unit of a tertiary hospital. Patients: Participants included prevalent patients treated with hemodialysis. All patients were above 18 years. Only patients with residual kidney function below 200 mL/24 hours were included to avoid bias. Measurements: Muscle strength was measured by handgrip strength (HGS). Each patient repeated 3 measurements, and the highest value was recorded. Handgrip strength cutoffs for low muscle strength were defined as <27 kg in men and <16 kg in women. Biochemical parameters, including serum phosphate level, were driven from routine monthly blood tests. Hyperphosphatemia was defined as serum phosphate above 4.5 mg/dL. Methods: Handgrip strength results were compared to nutritional, anthropometric, and biochemical parameters-in particular phosphate level. Long-term mortality was recorded. Results: Seventy-four patients were included in the final analysis. Handgrip strength was abnormally low in 33 patients (44.5%). Patients with abnormal HGS were older and more likely to have diabetes mellitus and lower albumin and creatinine levels. There was no correlation between HGS and phosphate level (r = 0.008, P = .945). On multivariable analysis, predictors of higher HGS were body mass index and creatinine. Diabetes mellitus and female sex predicted lower HGS. Hyperphosphatemia correlated with protein catabolic rate, blood urea nitrogen, and creatinine. On multivariable analysis, predictors of hyperphosphatemia were higher creatinine level, normal albumin level, and heart failure. During mean follow-up time of 7.66 ± 3.9 months, 11 patients died. Mortality was significantly higher in patients with abnormally low HGS compared with normal HGS (odds ratio = 9.32, P = .02). Limitations: A single-center study. All measurements were performed at one time point without repeated assessments. Direct dietary intake, degree of physical activity, and medication compliance were not assessed. Conclusion: Hyperphosphatemia correlated with increased protein intake as assessed by protein catabolic rate in patients treated with hemodialysis; however, neither correlated with higher muscle strength as measured by HGS.Trial registration: MOH 202125213.

Contexte: La sarcopénie, qui est fréquemment observée chez les patients traités par hémodialyse, est corrélée à de faibles taux sériques de phosphate. Dans ce contexte, la normophosphatémie est souhaitée, mais la restriction alimentaire en phosphate est difficile à réaliser et peut entraîner une restriction indésirable en protéines. Objectif: Notre objectif était de déterminer si l'hyperphosphatémie est associée à une plus grande force musculaire chez les patients qui reçoivent un traitement par hémodialyse. Conception: Étude observationnelle prospective monocentrique. Cadre: Le service de dialyse d'un hôpital de soins tertiaires. Sujets: Des patients prévalents âgés de plus de 18 ans qui recevaient des traitements d'hémodialyse en ambulatoire dans le service de dialyse de l'hôpital. Afin de limiter les biais, seuls les patients avec une fonction rénale résiduelle inférieure à 200 ml/24 heures ont été inclus. Mesures: La force musculaire a été mesurée par le test de force de préhension (HGS - handgrip strength). Trois mesures ont été faites pour chaque patient et la valeur la plus élevée a été enregistrée. Les seuils de faible force musculaire à l'HGS ont été établis à < 27 kg pour les hommes et à < 16 kg pour les femmes. Les paramètres biochimiques, notamment le taux de phosphate sérique, ont été déterminés à partir des analyses sanguines mensuelles des patients. L'hyperphosphatémie a été définie par une concentration sérique en phosphate supérieure à 4,5 mg/dl. Méthodologie: Les résultats de l'HGS ont été comparés aux paramètres nutritionnels, anthropométriques et biochimiques ­ plus particulièrement au taux de phosphate. La mortalité à long terme a été enregistrée. Résultats: Soixante-quatorze patients ont été inclus dans l'analyse finale. Les résultats de l'HGS étaient anormalement faibles chez 33 patients (44,5 % des sujets). Les patients qui avaient obtenu un résultat anormal à l'HGS étaient plus âgés, plus susceptibles de souffrir de diabète, et présentaient des taux d'albumine et de créatinine plus faibles. Aucune corrélation n'a été observée entre le résultat à l'HGS et le taux sérique de phosphate (r=0.008; p=0.945). Dans l'analyse multivariée, l'indice de masse corporelle et le taux de créatinine étaient des prédicteurs d'un résultat plus élevé à l'HGS, alors que le diabète et le fait d'être une femme étaient prédictifs d'un résultat inférieur à l'HGS. L'hyperphosphatémie a été corrélée au taux de catabolisme des protéines, à l'urée et au taux de créatinine. Dans l'analyse multivariée, un taux de créatinine plus élevé, un taux d'albumine normal et une insuffisance cardiaque étaient des facteurs prédictifs d'une hyperphosphatémie. Au cours de la période moyenne de suivi (7,66 ± 3,9 mois), 11 patients sont décédés. La mortalité était significativement plus élevée chez les patients qui présentaient un résultat anormalement faible à l'HGS par rapport à la normale (RC: 9,32; p = 0,02). Limites: L'étude a été menée dans un seul centre. Toutes les mesures ont été effectuées à un moment donné sans évaluations répétées. L'apport alimentaire direct, le degré d'activité physique et l'observance des médicaments n'ont pas été évalués. Conclusion: Chez des patients traités par hémodialyse, l'hyperphosphatémie est corrélée à une augmentation de l'apport en protéines évalué par le taux de catabolisme des protéines, mais ni l'une ni l'autre n'est corrélée à une plus grande force musculaire mesurée par HGS.

Reduction of peritoneal dialysis associated infections using a novel exit-site care practice.

INTRODUCTION: Peritoneal dialysis (PD) related infections are a significant obstacle leading to PD discontinuation. Since catheter related infections (CRI), defined as exit site infections and/or tunnel infection, can progress to peritonitis, vigorous efforts are implemented in CRI prevention. Following an increased CRI rate in our institution, partially related to environmental organisms found in water distribution systems, we hypothesized that exit site care that includes prevention of water exposure-related pathogens may reduce CRI. METHODS: In this prospective single center study, we compared a contemporary cohort consisting of PD patients who implemented the modified exit-site care protocol, mainly including water avoidance during shower with stoma bag usage and local Mupirocin ointment against a historical control group before the protocol implementation. The historical cohort was allowed water exposure and used local gentamicin ointment. The primary outcome was the development of a CRI. Secondary outcomes were PD associated peritonitis and infection related outcomes. RESULTS: There were 55 patients in contemporary cohort and 58 in historical group. The CRI rate was significantly lower in study group (0.11/episodes per patient year [EPP]) compared to control group (0.71 EPP), p < 0.001. A multivariate Cox regression analysis demonstrated a protective effect of being in the contemporary cohort compared to historical group (HR for first CRI = 12.0 95%CI: 4.0-35.7, p < 0.001). Peritonitis rate was significantly lower in contemporary cohort (0.19/EPP) compared to the historical group (0.40/EPP), p = 0.011. Transfer to hemodialysis was significantly lower in contemporary cohort than historical group (7.3% vs 31.0% in contemporary and historical group respectively, HR = 0.2, 95%CI; 0.05-0.6, p = 0.001). CONCLUSION: An exit site care protocol that includes water avoidance and local Mupirocin use reduced substantially both CRI and peritonitis rate in patients treated with PD.

Long-Term Outcomes of Nephrectomy Before Kidney Transplantation in Patients With Polycystic Kidney Disease.

BACKGROUND: Polycystic kidney disease (PKD) is the most common hereditary kidney disorder. In most patients, the disease progresses to end stage kidney disease, which is treated preferably by kidney transplantation. In certain clinical circumstances, a pretransplant nephrectomy is indicated. Data regarding long-term outcomes of pretransplant nephrectomy are limited. In this study, we aimed to compare patient and graft survival, as well as other long-term outcomes of kidney transplantation, between patients with PKD who had a pretransplant nephrectomy and those who have not. METHODS: A retrospective analysis of 112 adult kidney transplant recipients with PKD, 36 (32.14%) of which underwent a pretransplant nephrectomy. RESULTS: In a mean follow-up period of 79 and 129 months (for patients who underwent nephrectomy and patients who did not, respectively), no significant differences were found in patient and graft survival, after adjustment to age and donor type. In addition, rate of hospitalizations, urinary tract infections requiring hospitalization, diabetes mellitus, and erythrocytosis post-transplant were similar in both cohorts. CONCLUSIONS: Pretransplant nephrectomy in patients with PKD is not associated with increased risk of mortality and other long-term complications following kidney transplantation.

Medical cannabis for pain management in patients undergoing chronic hemodialysis: randomized, double-blind, cross-over, feasibility study.

Background: Chronic pain is prevalent but difficult to treat in patients undergoing hemodialysis (HD). Effective and safe analgesics are limited in this patient population. Our aim in this feasibility study was to evaluate the safety of sublingual oil based medical cannabis for pain management in patients undergoing HD. Methods: In a prospective randomized, double-blind, cross-over design, patients undergoing HD with chronic pain were assigned to one of three arms: BOL-DP-o-04-WPE whole-plant extract (WPE), BOL-DP-o-04 cannabinoid extraction (API) or placebo. WPE and API contained trans-delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:6 ratio (1:6, THC:CBD). Patients were treated for 8 weeks, with subsequent 2-week wash out, followed by a cross-over to a different arm. The primary endpoint was safety. Results: Eighteen patients were recruited and 15 were randomized. Three did not complete drug titration period due to adverse events (AEs) and one patient died during titration due to sepsis (WPE). Of those who completed at least one treatment period, seven patients were in the WPE arm, five in the API and nine receiving placebo. The most common AEs were sleepiness, which improved after dose reduction or patient adaptation. Most AEs were mild to moderate and resolved spontaneously. Serious AEs considered related to study drug included one episode of accidental overdose (WPE) leading to hallucinations. Liver enzymes were stable during cannabis treatment. Conclusions: Short-term medical cannabis use in patients treated with HD was generally well tolerated. The safety data supports further studies to assess the overall risk-benefit of a treatment paradigm utilizing medical cannabis to control pain in this patient population.

Risk factors, clinical characteristics and prognostic value of acute kidney injury in COVID-19 compared with influenza virus and respiratory syncytial virus.

BACKGROUND: Acute Kidney Injury (AKI) complicates a substantial part of patients with COVID-19. Direct viral penetration of renal cells through the Angiotensin Converting Enzyme 2 receptor, and indirect damage by the aberrant inflammatory response characteristic of COVID-19 are likely mechanisms. Nevertheless, other common respiratory viruses such as Influenza and Respiratory Syncytial Virus (RSV) are also associated with AKI. METHODS: We retrospectively compared the incidence, risk factors and outcomes of AKI among patients who were admitted to a tertiary hospital because of infection with COVID-19, influenza (A + B) or RSV. RESULTS: We collected data of 2593 patients hospitalized with COVID-19, 2041 patients with influenza and 429 with RSV. Patients affected by RSV were older, had more comorbidities and presented with higher rates of AKI at admission and within 7 days (11.7% vs. 13.3% vs. 18% for COVID-19, influenza and RSV, respectively p = 0.001). Nevertheless, patients hospitalized with COVID-19 had higher mortality (18% with COVID-19 vs. 8.6% and 13.5% for influenza and RSV, respectively P < 0.001) and higher need of mechanical ventilation (12.4% vs. 6.5% vs.8.2% for COVID-19, influenza and RSV, respectively, P = 0.002). High ferritin levels and low oxygen saturation were independent risk factors for severe AKI only in the COVID-19 group. AKI in the first 48 h of admission and in the first 7 days of hospitalization were strong independent risk factors for adverse outcome in all groups. CONCLUSION: Despite many reports of direct kidney injury by SARS-COV-2, AKI was less in patients with COVID-19 compared to influenza and RSV patients. AKI was a prognostic marker for adverse outcome across all viruses.

The Long-Term Outcome of Kidney Transplant Recipients in the Eighth Decade Compared With Recipients in the Seventh Decade of Life.

BACKGROUND: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation. METHODS: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors. RESULTS: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01). CONCLUSIONS: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation.

The impact of normal range estimated glomerular filtration rate on mortality in selected patients undergoing coronary angiography - a long-term follow-up.

BACKGROUND: Estimated glomerular filtration rate (eGFR) predicts mortality and adverse cardiovascular events in people with chronic kidney disease. The significance of eGFR within the normal range and its long-term effect on clinical adverse events is unknown. We examined the effect of normal range or mildly reduced eGFR on long-term mortality in a large prospective registry. METHODS: The study included consecutive patients undergoing clinically-driven coronary angiography who had an eGFR ≥60 ml/min/1.73 m2. Baseline clinical characteristics were assessed, and patients were followed-up for the occurrence of all-cause mortality. Cox regression analysis was used to evaluate the impact of eGFR. RESULTS: A total of 4186 patients were recruited. Median follow-up time was 2883 days (7.9 years). Mean age was 62.0 ± 11.3 years with 77.4% males. Clinical presentation included acute coronary syndrome and stable angina. In a multivariable model adjusted for possible confounding factors, decreasing eGFR within the normal and mildly reduced range was inversely associated with long-term all-cause mortality with a hazard ratio (HR) of 1.32 for every decrease of 10 ml/min/1.732 in eGFR. Compared to eGFR > 100 ml/min/1.732, there was a graded association between lower eGFR values and increased long term mortality with a HR of 1.16 (0.59-2.31) for eGFR 90-100 ml/min/1.732, HR 1.54 (0.81-2.91) for eGFR 80-90 ml/min/1.732, HR 2.62 (1.41-4.85) for eGFR 70-80 ml/min/1.732 and HR 2.93 (1.58-5.41) for eGFR 60-70 ml/min/1.732. CONCLUSION: eGFR within the normal and mildly reduced range is an independent predictor of long-term all-cause mortality in selected patients undergoing clinically driven coronary angiography.

Assessment of Kidney Function After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. OBJECTIVE: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. DESIGN: This is a prospective single center study. SETTING: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. PATIENTS: The cohort included 1321 patients who underwent TAVR. MEASUREMENTS: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. METHODS: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. RESULTS: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). LIMITATIONS: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. CONCLUSIONS: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.

CONTEXTE: L'implantation transcathéter de valvule aortique (ITVA), bien qu'elle soit associée à un risque accru d'insuffisance rénale aiguë (IRA), est susceptible d'améliorer la fonction rénale. OBJECTIFS: Évaluer l'ampleur de l'amélioration de la fonction rénale (AFR) après une ITVA et évaluer son incidence sur le taux de mortalité à long terme. TYPE D'ÉTUDE: Étude prospective menée dans un seul centre hospitalier. CADRE: Le service de cardiologie, unité interventionnelle, d'un centre de soins tertiaires. SUJETS: La cohorte était constituée de 1 321 patients ayant subi une ITVA. MESURES: Le taux de créatinine sérique a été mesuré à l'inclusion, avant l'intervention et pour les 7 jours suivants, ou jusqu'au congé du patient. MÉTHODOLOGIE: L'AFR a été définie comme l'image miroir de l'IRA, soit une réduction de plus de 0,3 mg/dl du taux de créatinine après l'intervention par rapport au taux minimum de créatinine mesuré pré-ITVA, ou un rapport entre la créatinine minimale post-ITVA et la créatinine pré-ITVA inférieur à 0,66 jusqu'à 7 jours après l'intervention. Les patients ont été classés en trois groupes et comparés selon des critères cliniques en fonction de la modification de la fonction rénale après l'intervention : un groupe AFR, un groupe IRA et un groupe « fonction rénale préservée ¼ (FRP). Le critère principal était la mortalité toutes causes confondues. RÉSULTATS: L'incidence d'une AFR était de 5 % et elle s'est avérée mineure et d'importance clinique incertaine pour 55 des 66 patients concernés. La proportion de patients atteints d'IRA était de 19,1 %. Après l'analyse multivariée, un débit de filtration glomérulaire estimé (DFGe) inférieur à 60 ml/min/1,73 m2 s'est avéré un facteur prédictif de l'AFR [rapport de cotes pour une AFR : 0,93 (IC : 0,91-0,95; p < 0,001)]. Les patients du groupe AFR présentaient un score de la Society of Thoracic Surgery (STS) plus élevé que ceux des autres groupes. Le taux de mortalité était similaire pour les groupes AFR et FRP (respectivement 43,9 % et 33,8 %), mais s'est avéré significativement plus élevé dans le groupe IRA (60,7 %; p < 0,001). LIMITES: Manque de consensus autour de la définition d'une amélioration de la fonction rénale dans les différentes études.Étude menée dans un seul centre.Bien que les données aient été recueillies de façon prospective, le plan d'analyse n'a été défini qu'après la collecte des données. CONCLUSION: L'amélioration de la fonction rénale après l'ITVA n'était pas un phénomène courant dans notre cohorte et n'a pas permis de réduire le taux de mortalité global.

Chronic pain is underestimated and undertreated in dialysis patients: A retrospective case study.

Significant chronic pain is highly prevalent in chronic kidney disease patients and is associated with morbidity and mortality. In this study, we retrospectively evaluated the incidence and treatment of pain in the dialysis unit of our tertiary referral center. The cohort included 147 patients. Over 66% reported significant (VAS >40) chronic pain during the preceding 3 months, most often characterized as stabbing (38%) and with concurrent itching (44%). Only 33% of patients received chronic pain medications, while 55.6% of patients with severe pain and 45.9% with pain characterized as the worst imaginable did not receive any analgesics. Pregabalin or weak opioids were the most frequently used. In conclusion, chronic pain is highly prevalent and markedly undertreated in dialysis patients, despite its significant adverse impact.

Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family with a New Recessive Mutation (S553L) Compared to a Family with a Dominant Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter.

BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described. METHODS: Clinical and genetic investigation of members of 2 families was performed, one with recessive FHHt, and the other, an expansion of a family with Q309R KLHL3 dominant mutation, previously reported by us. Urinary exosomal sodium chloride cotransporter (NCC) was measured. RESULTS: A family with recessive FHHt caused by a new KLHL3 mutation, S553L, is described. This consanguineous Jewish family of Yemenite extraction, included 2 homozygous and 7 heterozygous affected subjects. Increased urinary NCC was found in the affected members of the family with dominant Q309R KLHL3 mutation. In the recessive S553L family, homozygotes appeared to have increased urinary NCC abundance. Surprisingly, heterozygotes seemed to have also increased urinary NCC, though at an apparently lower degree. This was not accompanied by a clinical phenotype. CONCLUSIONS: A new recessive mutation in KLHL3 (S553L) was identified in FHHt. Increased urinary NCC was found in affected members (heterozygous) with dominant KLHL3 Q309R, and in affected members (homozygous) of the recessive form. Unexpectedly, in the recessive disease, heterozygotes seemed to have increased urinary NCC as well, apparently not sufficient quantitatively to produce a clinical phenotype.