Abnormal inpatient EEG predicts seizure occurrence independently of renal function.

Purpose: The study aimed to determine prospectively whether there is a significant relationship between renal function as per the estimated glomerular filtration rate (eGFR), and the occurrence of seizures in patients who have no history of epilepsy and who required an EEG while hospitalized. Methods: Adult patients who were hospitalized at Hôtel-Dieu de France University Hospital in Beirut and who required routine EEGs were included over a period of 13 months. We excluded critical patients or those with history of epilepsy.Data was analyzed depending on the EEG result and according to the baseline eGFR estimated by the CKD-EPI formula. Patients were followed prospectively by phone interview at 6 months for occurrence of seizure or death. Results: Sixty one patients with a mean age of 66 (age range 19 to 95) were included (52 % were females). Of the 23 patients who had normal EEGs, 43.47% had abnormal eGFR, and none of them had a seizure. Of the patients with abnormal EEGs, 71.05% had abnormal eGFR, of which 7 had seizures. A significant relationship was found between having an abnormal EEG and the risk of developing a seizure in the future independently of the baseline eGFR.Whatever the eGFR is, if the EEG is normal, there will be lower risk to develop a seizure at 6 months. Conclusions: While eGFR and the incidence of seizures were not directly related, our study showed that patients with abnormal EEG were more likely to develop seizures regardless of their baseline eGFR.

Anemia biomarkers and mortality in hemodialysis patients with or without diabetes: A 10-year follow-up study.

BACKGROUND: Many studies have assessed the association between anemia and mortality in hemodialysis but few compared patients with and without diabetes. Our study aims to investigate the impact of hemoglobin and iron parameters on mortality in hemodialysis patients with or without diabetes. METHODS: This is a two-center retrospective study that included all adult patients who started hemodialysis between February 2012 and February 2020, followed until January 2021. Averages of hemoglobin, ferritin and transferrin saturation of entire follow-up were recorded. Kaplan Meier survival, log rank test and cox regression analyses were performed to assess the association between anemia biomarkers and mortality. RESULTS: A total of 214 patients were included. Mean age was 67.98 ±12.41 years, mean hemoglobin was 10.92 ±0.75 g/dL, mean ferritin was 504.43 ± 221.42 ng/mL and mean transferrin saturation was 26.23 ±7.77%. Log rank test showed an association between hemoglobin ≥11 g/dL and better survival in patients without diabetes (P = 0.028). Based on cox regression analysis, hemoglobin was associated with all-cause mortality in all patients (HR = 0.66; CI:0.49,0.89; P = 0.007). When comparing patients with and without diabetes, this association remained significant only in patients without diabetes (HR = 0.53; CI:0.37,0.77; P<0.001). Based on different multivariate models, hemoglobin, ferritin and age were independent factors associated with mortality in patients without diabetes. CONCLUSIONS: This study showed that hemoglobin ≥11 g/dL is associated with better survival in hemodialysis patients without diabetes but not in those with diabetes. These differences need to be further explored in other countries and settings. An individualization of the hemoglobin target level might be necessary to improve patients' outcomes.

Routine laboratory testing in hemodialysis: how frequently is it needed?

BACKGROUND: Hemodialysis patients are followed by routine laboratory testing. There is uncertainty whether these tests always lead to a change in decision-making. This study aims to discover the number of yearly interventions/changes in prescription based on these tests and depict the group of patients who would benefit from reduced or increased laboratory blood tests. METHODS: This is a multi-center retrospective study that included patients on hemodialysis for more than one year. Laboratory data collected included yearly average of hemoglobin, urea reduction ratio (URR), serum phosphate, calcium, potassium, parathormone (PTH), ferritin and transferrin saturation (TSAT); changes in prescription of erythropoietin-stimulating agents (ESAs), intravenous (IV) iron, alfacalcidol, phosphate binders and dialysis parameters were retrieved from medical records. A multivariate regression analysis assessed factors associated with high number of interventions. RESULTS: A total of 210 hemodialysis patients were included: 62.4% males, 47.1% diabetics. Their median age was 72 (62,78.5) years. Their laboratory parameters were within KDIGO targets. The median number of yearly interventions was 5 (3,7) for ESAs, 4 (2,6) for IV iron, 1 (0,2.25) for phosphate binders, 0 (0,1) for alfacalcidol. Based on the multivariate analysis, patients with higher ferritin, frequent changes in ESA, more changes in alfacalcidol and higher PTH had higher number of prescription's changes in ESA, IV iron, phosphate binders and alfacalcidol respectively. CONCLUSION: While maintaining KDIGO targets, therapeutic interventions following routine laboratory testing did not exceed six times yearly for all parameters. This suggests that a reduced testing frequency in hemodialysis patients is possible without any impact on quality of care. A personalized approach remains safe for hemodialysis patients while reducing the cost. This is very relevant in low-resource settings and during economic crises and needs to be evaluated in prospective studies.

Late antibody-mediated rejection in a kidney transplant recipient: COVID 19 induced?

BACKGROUND: Antibody-mediated rejection (AMR) was described in kidney transplant patients after viral infections, such as the cytomegalovirus. Very few cases were recently reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, probably in the context of lowering of immunosuppressive therapy. To date, no direct immunological link was proved to explain a connection between the coronavirus disease 19 (COVID-19) infection and antibody-mediated rejection (AMR) if it exists. CASE PRESENTATION: Here we try to find this association by presenting the case of a low immunological risk patient who presented, six years post-transplant, with c4d negative antibody mediated rejection due to an anti-HLA-C17 de novo donor specific antibody (DSA) after contracting the coronavirus disease 19. The HLA-Cw17 activated the antibody-dependent cell-mediated cytotoxicity via the KIR2DS1 positive NK cells. DISCUSSION AND CONCLUSIONS: This case report may prove a direct role for COVID-19 infection in AMRs in the kidney transplant recipients, leading us to closely monitor kidney transplant recipients, especially if they have "at-risk" donor antigens.

An Unusual Course of a 2,8-Dihydroxyadeninuria Crystalline Nephropathy Secondary to Adenine Phosphoribosyltransferase Deficiency.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder caused by an autosomal recessive genetic disease leading to the deposition of 2,8-dihydroxyadenine (2,8-DHA) in the kidney. The disease remains under-recognized, oftentimes diagnosed in late stages of renal insufficiency or a failed kidney allograft with biopsy-proven disease recurrence. Here, we present the case of a 59-year-old middle eastern male patient diagnosed with 2,8-DHA nephropathy after a very unusual presentation, and we show how the initiation of an appropriate therapy slowed down his evolution toward kidney replacement therapies. His disease was found to be secondary to a specific APRT gene variant c.188G>A p (Gly63Asp) also described in 4 other patients, all from middle eastern origins.

Age and multimorbidities as poor prognostic factors for COVID-19 in hemodialysis: a Lebanese national study.

BACKGROUND: Hemodialysis patients with COVID-19 have been reported to be at higher risk for death than the general population. Several prognostic factors have been identified in the studies from Asian, European or American countries. This is the first national Lebanese study assessing the factors associated with SARS-CoV-2 mortality in hemodialysis patients. METHODS: This is an observational study that included all chronic hemodialysis patients in Lebanon who were tested positive for SARS-CoV-2 from 31st March to 1st November 2020. Data on demographics, comorbidities, admission to hospital and outcome were collected retrospectively from the patients' medical records. A binary logistic regression analysis was performed to assess risk factors for mortality. RESULTS: A total of 231 patients were included. Mean age was 61.46 ± 13.99 years with a sex ratio of 128 males to 103 females. Around half of the patients were diabetics, 79.2% presented with fever. A total of 115 patients were admitted to the hospital, 59% of them within the first day of diagnosis. Hypoxia was the major reason for hospitalization. Death rate was 23.8% after a median duration of 6 (IQR, 2 to 10) days. Adjusted regression analysis showed a higher risk for death among older patients (odds ratio = 1.038; 95% confidence interval: 1.013, 1.065), patients with heart failure (odds ratio = 4.42; 95% confidence interval: 2.06, 9.49), coronary artery disease (odds ratio = 3.27; 95% confidence interval: 1.69, 6.30), multimorbidities (odds ratio = 1.593; 95% confidence interval: 1.247, 2.036), fever (odds ratio = 6.66; 95% confidence interval: 1.94, 27.81), CRP above 100 mg/L (odds ratio = 4.76; 95% confidence interval: 1.48, 15.30), and pneumonia (odds ratio = 19.18; 95% confidence interval: 6.47, 56.83). CONCLUSIONS: This national study identified older age, coronary artery disease, heart failure, multimorbidities, fever and pneumonia as risk factors for death in patients with COVID-19 on chronic hemodialysis. The death rate was comparable to other countries and estimated at 23.8%.

Effective treatment with Tocilizumab in a COVID-19 patient on maintenance hemodialysis: A case report.

Coronavirus disease 2019 (COVID-19) is a rapidly spreading infective disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2). The management of this disease remains a challenge particularly in certain subgroups of patients such in hemodialysis patients who have higher exposure rates due to the nature of their in-hospital care, and higher mortality due to their burden of comorbidities. We report a case of a 52-year-old patient with Von Hippel Lindau syndrome and end-stage renal disease on hemodialysis who contracted COVID-19 infection. Despite the patient's rapidly deteriorating clinical status he was successfully treated with Tocilizumab, after which he showed rapid improvement in his clinical, biological and radiological parameters. Although few studies were available regarding the use of Tocilizumab in the dialysis population, its use proved to be effective and well tolerated in our patient.

Exploring the knowledge gap of immune checkpoint inhibitors in chronic renal failure: A systematic review of the literature.

Targeting the immune system with immune checkpoint inhibitors (ICI) to treat cancer has been lately adopted with a significant improvement of patients' survival. In parallel, the incidence of malignancy in chronic kidney disease (CKD) patients is increasing, but solid evidence concerning the efficacy and safety of ICI in this population is lacking. Moreover, the use of these agents as immunity boosters in kidney graft recipients treated with immunosuppressors is still controversial. We present in this article a review of the pharmacological properties of these drugs and their behavior with kidney failure and dialysis, as well as evidence of their use in different populations of CKD. Most of the available data are limited to case reports and case series. These drugs appear to be safe without dose adjustment in CKD patients and patients on dialysis. A major concern with this therapy in transplanted patients remains the risk of graft rejection.

Musculoskeletal disorders in hemodialysis patients: different disease clustering according to age and dialysis vintage.

Musculoskeletal disorders remain a major problem in hemodialysis patients. The aim of the study was to estimate the prevalence of musculoskeletal manifestations in hemodialysis patients and identify disease cluster profiles. We performed a cross-sectional study including all adult patients in the hemodialysis unit at Hotel-Dieu de France Hospital. We collected demographic characteristics, musculoskeletal symptoms, biologic parameters, and treatments. Musculoskeletal disorders were classified by a rheumatologist into predefined diagnostic categories. Prevalence was presented, and a cluster analysis was performed. Eighty-nine patients were included, mean age was 67.5 ± 12 years, and 43.8% were female. Dialysis vintage was 5.7 ± 5.37 years. Musculoskeletal symptoms were reported by 76.4% of the patients. Pain was the most frequent symptom (44.9%). The main diagnoses were osteoarthritis (53.9%) and fracture (27%). Musculoskeletal symptoms and disorders were significantly associated with dialysis vintage and age. Cluster analysis identified three patient profiles: younger with low calcium levels, younger but long dialysis vintage with osteoarthritis and carpal tunnel syndrome, and older with long dialysis vintage and fractures. The prevalence of musculoskeletal manifestations is high in the hemodialysis population and increases with dialysis vintage. Musculoskeletal disorders cluster according to age and dialysis vintage. Key Points• Musculoskeletal symptoms are highly prevalent among hemodialysis patients (76.4%).• All musculoskeletal disorders are associated with dialysis vintage and age.• Three clusters are identified among hemodialysis patients: young with low calcium levels, young but long dialysis vintage with osteoarthritis and carpal tunnel syndrome and old with long dialysis vintage with fractures.

Evaluation of chronic kidney disease in cancer patients: is there a preferred estimation formula?

BACKGROUND: The evaluation of chronic kidney disease (CKD) in cancer patients seems to rely mostly on the Cockcroft-Gault (CG) formula or the creatinine levels to adjust treatment dosages which is a practice refuted by internists. AIMS: We evaluate the overall agreement of the CG, modification of diet in renal disease (MDRD) and CKD-epidemiology collaboration equations (CKD-EPI) equation with the newly devised Janowitz and Williams' (JW) equation. METHODS: The renal function was estimated in 235 cancer patients according to the CG, MDRD, body surface area (BSA)-adjusted MDRD, CKD-EPI, BSA-adjusted CKD-EPI and JW formulae. RESULTS: JW equation was more in agreement with CG and CKD-EPI estimations than the other equations. Taking JW equation as reference, receiver operating characteristic curve analysis showed that CG eGFR had the higher area under the curve when compared with other equations. Hierarchical cluster analysis showed more proximity between CG and JW equations than the other equations. CONCLUSION: The newly proposed JW eGFR estimation was more in agreement with CG equation than the other equations.

High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial.

BACKGROUND: Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score. METHODS: This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 µg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks. RESULTS: At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01). CONCLUSION: Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 µg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K2 over a longer follow-up period. TRIAL REGISTRATION: The clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354 , on August 11, 2016).

[Successful familial kidney transplant in an infant weighing less than 10 kg: case report and review of the literature]. / SUCCÈS D'UNE GREFFE RÉNALE PÉDIATRIQUE CHEZ UN NOURRISSON DE POIDS INFÉRIEUR À 10 Kg: Cas clinique et revue de la littérature.

We report the case of a Lebanese infant born by normal delivery at 40 weeks of gestation. Weight and height at birth were 3200 grams and 49 cm respectively. Serum creatinine in the first week of life was 323 mmol/l (normal value for age is less than 20 mmol/l). Kidney ultrasound confirmed diagnosis of hypoplastic small kidneys. Conservative treatment of renal failure was initiated from the first days of life. Conservative management of renal failure included careful attention to fluid balance, maintenance of adequate nutrition and correction of hyperkalemia, acidosis, hyperphosphatemia and prevention of renal osteodystrophy by the use of dietary phosphate binders and vitamin D analogs. After a slight decrease of serum creatinine in the first three months of life, creatininemia increased progressively despite conservative treatment associated to hyperkalemia and severe pruritis due to hyperphosphatemia. Faced with the progression of renal failure, we decided to start automated peritoneal dialysis at seven months of life. Weight and height were respectively 6200 g and 63 cm. Serum creatinine was 432 mmol/L. Pruritis improved after starting peritoneal dialysis as well as appetite. At 20 months of life and a weight of 9.7 kg, a familial kidney transplant was performed. Immunosuppressive treatment included SimulectO, on day 1 and day 4, associated to mycophenolate mofetil, tacrolymus and prednisolone. The immediate post-transplant period was complicated by urinay tract infection due to BSLE E. coli. After four episodes of urinary tract infection due to resistant E coli associated to a non obstructive stone of 15 mm in the allograft kidney, we performed two sessions of lithotripsy and placed a double J stent. Biochemical urinary analysis did not reveal any causes for lithiasis. Stone disappeared as well as infection after lithotripsy. Renal function is normal for age one year after the kidney transplant. To our knowledge, this is the first reported case of a successful kidney transplant in a Lebanese infant with kidney failure since birth with kidney transplant performed at less than 10 kg of weight on the transplant day. Peritoneal dialysis is the treatment of choice for infants with chronic kidney failure. Familial or cadaveric kidney transplant should be encouraged and performed even in infants weighing less than 10 kg allowing them to have normal growth as well as social and school integration.

[Kidney transplantation in pediatric patients: 18-year experience at Hôtel-Dieu de France]. / LA TRANSPLANTATION RÉNALE CHEZ L'ENFANT Dix-huit ans d'expérience à l'Hôtel-Dieu de France.

INTRODUCTION: During the period from September 1993 to March 2011, 79 kidney transplants in children and adolescents less than 18 years old were performed in our department; fifty-six in the familial group and 13 in the cadaveric group. We report in this study: immunosuppression protocols, medical and surgical complications (including rejection episodes), graft and patient survival. MATERIAL AND METHODS: Immunosuppression protocol has been modified throughout those eighteen years. Induction therapy includes serum anti- lymphocyte + cyclosporine + azathioprine and prednisone. Since 2000, azathioprine was replaced by mycophenolate mofetil and since January 2005 cyclosporine was given as well as tacrolymus according to EBV status. Basiliximab-Simulect® was included in the protocol since 2010. RESULTS: Surgical complications were only two lymphoceles, reversible after surgical drainage in the peritoneum. Medical complications were mainly infections or rejections. Thirty-six episodes of rejection occurred: 7 in the commercial group, 16 in the familial group and 13 in the cadaveric group. At the end of the study, 9 patients returned to dialysis, 5 from the cadaveric group, 2 from the familial group and 2 from the commercial group. CONCLUSION: After eighteen years experience in kidney transplant, we believe that kidney transplant remains the optimal treatment for terminal renal failure even for children weighing less than 10 kg. The follow-up of pediatric patients with kidney transplant revealed different positive effects on growth, regular school attendance and psychomotor development. At the end of the study: 24 are at school, 12 at universities, 5 are attending specialized schools and 9 are active workers.

DONOR SPECIFIC ANTI-HLA ANTIBODIES DETECTION AND IMPACT IN KIDNEY TRANSPLANTATION.

Kidney transplantation is now accepted to be the best treatment for end-stage renal disease. Despite the improvement of immunosuppressive therapy, there is still actually substantial loss of allografts, in part due to uncontrolled humoral immunity. For many years, the primary technique for the detection of anti-HLA antibodies was the CDC (complement dependent cytotoxicity). The recent use of solid phase assays, mainly the Luminex technology allowed detection of antibodies at much lower levels, and it has been shown that these antibodies have negative impact on the graft survival. We herein review the principal techniques for anti-HLA detection and the different presentations of humoral rejection.

[Immunosuppressive protocols in kidney transplantation: with or without induction?]. / PROTOCOLES D'IMMUNOSUPPRESSION EN TRANSPLANTATION RNALE: AVEC OU SANS INDUCTION?

Kidney transplantation is the treatment of choice of end stage kidney disease. Over the years, kidney transplantation progressed tremendously, mainly by the improvement of immunosuppressive drugs used in the prevention of acute rejection. Since the introduction of cyclosporine in the 80s, many immunosuppressive protocols have been established. These protocols are characterized by two strategies: with or without induction. The agents used in induction therapies can be polyclonal or monoclonal antibodies. The decision of using induction therapy relies mainly on the evaluation of the immunological risk in the recipient. Even if protocols with induction have improved early results concerning acute rejection, the protocoles without induction seem justified in some candidates. The optimal immunosuppressive protocol is not yet established, and individualization of immunosuppressive treatment is necessary.

[Plasma creatinine, Cockcroft and MDRD: validity and limitations for evaluation of renal function in chronic kidney disease]. / Mesure et estimation du débit de filtration glomérulaire : quels outils pour la prise en charge de la maladie rénale chronique ?

The glomerular filtration rate (GFR) is the best indicator of renal function. Measurement of the plasma creatinine level is the simplest laboratory test for estimating GFR. The plasma creatinine assay is currently being standardized, which will improve its reproducibility. It remains the best indicator for the diagnosis and follow-up of acute renal failure. Conversely, diagnosis and follow-up of chronic kidney disease are based on the GFR value, which is routinely estimated from formulas derived from plasma creatinine levels. The formula developed from the MDRD study performs better than the Cockcroft formula for nearly all patients and clinical situations and should replace it. GFR should be measured directly, by the urinary clearance of exogenous markers, in any situation in which the precision of the formula used is insufficient for medical decision-making. This requires defining for any given patient and situation both the desired precision and that expected from the formulas.