Erythrocytosis and CKD: A Review.

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia, which is very common in patients with chronic kidney disease (CKD), erythrocytosis is less frequent but requires specific understanding by health care professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality. Classic causes of erythrocytosis associated with CKD include cystic kidney diseases, kidney or other erythropoietin-secreting neoplasms, high-altitude renal syndrome, overdosage of erythropoietin-stimulating agents, androgen therapy, heavy smoking, chronic lung disease, obstructive sleep apnea, IgA nephropathy, post-kidney transplant erythrocytosis, renal artery stenosis, and congenital etiologies. After ruling out the common acquired causes of erythrocytosis and/or in the presence of suggestive parameters, primary erythrocytosis or polycythemia vera (PV) should be considered, and patients should be screened for JAK2V617F somatic mutation. The newest entity inducing erythrocytosis is linked to the use of sodium/glucose cotransporter 2 (SGLT2) inhibitors that hypothetically activate hypoxia-inducible factor 2α (HIF-2α) and in some cases unmask PV. This Review focuses on the pathogenesis, renal manifestations and management of PV, the pathophysiology of erythrocytosis induced by SGLT2 inhibitors and the relevance of timely JAK2 mutation screening in these patients.

Acknowledging the impact of seasonal blood pressure variation in hypertensive CKD and non-CKD patients living in a Mediterranean climate.

BACKGROUND: This study aims to assess seasonal blood pressure (BP) variation in chronic kidney disease (CKD) and non-CKD patients living in a Mediterranean climate, and to find out if this variation entails significant adjustment of treatment and if it impacts renal outcomes and mortality. METHODS: This retrospective study included all hypertensive patients seen between February 2006 and April 2020 in two Lebanese clinics. Regression analyses were used to assess the association of seasonal BP variability and treatment adjustment with eGFR change from baseline, dialysis initiation and death. RESULTS: A total of 398 patients of 64.2 ±13.9 years were followed for 51.1 ±44.3 months, 67% had eGFR< 60 mL/min. Mean systolic and diastolic BP was 137.7 ±14.7 and 76.5 ±9.5 mmHg respectively. Systolic and diastolic BP were significantly lower in the warm season in CKD and non-CKD patients (P<0.001). The majority (91.4%) needed seasonal treatment modifications. After adjustment to age, sex, baseline eGFR, BP and number of antihypertensive drugs, we found a significant loss of eGFR with treatment modifications in both seasons, double risk of dialysis with the increase of antihypertensive treatment in both seasons and a 2.5 more risk of death with reduced treatment in the warm season. CONCLUSION: This study confirmed the seasonal BP variability in CKD and non-CKD patients from a Mediterranean climate. All types of treatment adjustment were associated with eGFR loss. Low BP in the warm season was highly associated with death.

Association of renal resistive indices with kidney disease progression and mortality.

BACKGROUND: Renal resistive indices (RRI) have been shown to predict the progression of kidney disease. This study aims to evaluate the association of RRI with mortality and dialysis initiation after adjustment to therapeutic and life style interventions. METHODS: This is a retrospective study that included all chronic kidney disease patients followed for at least two years in three nephrology clinics between 2006 and 2019 and who had a RRI level in their files. Kaplan Meier and log rank test compared the survival of patients with normal versus high RRI. Cox regression analysis evaluated the association between RRI and death or dialysis initiation after adjustment to treatments and life style modifications. RESULTS: A total of 192 patients were analyzed: 68 had RRI < 0.7 and 124 had RRI ≥ 0.7. Their mean age was 66.5 ± 13.1 years at first visit, 78.1% were males. There was a negative correlation between baseline eGFR and RRI (p < 0.001; Spearman correlation coefficient = -0.521). The survival was significantly better in patients with RRI < 0.7 with a Log Rank test < 0.001. The univariate cox regression analysis showed a significant association between RRI and mortality (HR = 1.08; 95%CI: 1.04-1.11; p < 0.001) that remained significant after adjustment to cardiovascular risk factors and interventions such as salt reduction, blood pressure control, statins and RAAS inhibitors (HR = 1.04; 95%CI: 1.00-1.08; p = 0.036). Cox regression analysis showed a significant association between RRI and dialysis initiation (HR = 1.06; 95%CI 1.01-1.10; p = 0.011). CONCLUSION: Our study revealed that patients with an elevated RRI ≥ 0.7 are at a higher risk of mortality after adjustment to medications and lifestyle modifications. RRI can, according to this study, be considered as an independent prognostic factor in CKD patients.

Sleepiness and Health-Related Quality of Life Among Kidney Transplant Recipients in a Low-Middle Income Country: A Cross-Sectional Study.

This study aims to describe daytime sleepiness and health-related quality of life (HRQoL) among Lebanese kidney transplant (KT) recipients and to examine the medical, psychosocial and transplant factors related to them. It is a cross-sectional multi-center study involving KT recipients >18 years. Daytime sleepiness was assessed using ESS Questionnaire. HRQoL was measured using the SF-36 questionnaire. Social support was self-reported. A multivariable regression analysis evaluated factors associated with daytime sleepiness and HRQoL in our sample. 118 patients were recruited over a 2 years period. Excessive daytime sleepiness was prevalent in 12.7%. It was associated with Diabetes Mellitus (OR 3.97, 95% CI 0.94-16.81, p = 0.06) and obesity (OR 1.13, 95% CI 1.02, 1.27, p = 0.02). Social support and higher eGFR were associated with better scores on the MCS (ß 24.13 p < 0.001 and ß 0.26 p < 0.01) and the PCS (ß 15.48 p < 0.01 and ß 0.22 P 0.02). Conversely, depression and hospitalization were negatively associated with the MCS (ß -27.44, p < 0.01 and ß -9.87, p < 0.01) and the PCS (ß -0.28.49, p < 0.01 and ß -10.37, p < 0.01).

Stroke in hemodialysis patients and its association with CHA2DS2-VASC and HAS-BLED scores: a retrospective study.

Background: In the general population, the CHA2DS2-VASC and the HAS-BLED scores are helpful to predict cerebrovascular events and hemorrhage in patients with atrial fibrillation (AF). However, their predictive value remains controversial in the dialysis population. This study aims to explore the association between these scores and cerebral cardiovascular events in hemodialysis (HD) patients. Methods: This is a retrospective study including all HD patients treated between January 2010 and December 2019 in two Lebanese dialysis facilities. Exclusion criteria are patients younger than 18 years old and patients with a dialysis vintage less than 6 months. Results: A total of 256 patients were included (66.8% men; mean age 69.3 ± 13.9 years). The CHA2DS2-VASc score was significantly higher in patients with stroke (P = .043). Interestingly, this difference was significant in patients without AF (P = .017). Using receiver operating curve analysis, CHA2DS2-VASc score had an area under the curve (AUC) of 0.628 [95% confidence interval (CI): 0.539-0.718) and the best cut-off value for this score was 4. The HAS-BLED score was also significantly higher in patients with a hemorrhagic event (P < .001). AUC for HAS-BLED score was 0.756 (95% CI: 0.686-0.825) and the best cut-off value was also 4. Conclusions: In HD patients, CHA2DS2-VASc score can be associated with stroke and HAS-BLED score can be associated with hemorrhagic events even in patients without AF. Patients with a CHA2DS2-VASc score ≥4 are at the highest risk for stroke and adverse cardiovascular outcomes, and those with a HAS-BLED score ≥4 are at the highest risk for bleeding.

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.

Metformin-Associated Lactic Acidosis in a Diabetic Patient with Normal Kidney Function and Occult Cirrhosis.

Background: Lactic acidosis is a well-known complication of metformin accumulation in diabetic patients with kidney failure. However, it is not usual to raise the diagnosis of metformin-associated lactic acidosis when patients have normal kidney function. The causes of metformin-induced high lactate include the accumulation of normal doses of metformin in chronic kidney disease, an overdose of this drug without kidney failure, or an increase in lactate production due to the inhibition of liver gluconeogenesis. Case Presentation. We report the case of a 61-year-old diabetic man who was brought to the emergency room in a comatose state. His family reported abdominal pain with diarrhea in the last two days. He was found to have severe lactic acidosis with normal serum creatinine. He was on a regular dose of metformin, and his family denied any other medical history or any alcohol abuse. He showed no signs of infection, his liver enzymes were slightly elevated, and he had severe anemia. His hemodynamics deteriorated quickly within hours, and an abdominal computed tomography scan revealed no abnormalities. He underwent a laparotomy that ruled out mesenteric ischemia and revealed an abnormal liver. The liver biopsy later confirmed the diagnosis of cirrhosis. Conclusions: We discuss here the probable causes of severe lactic acidosis and the role of metformin in exacerbating this acid-base disturbance in cirrhotic patients. Future research is needed to determine whether these patients might benefit from dialysis.

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.

Cost of illness of chronic kidney disease in Lebanon: from the societal and third-party payer perspectives.

BACKGROUND: Chronic kidney disease (CKD) is the 12th leading cause of death worldwide. Cost-of-illness studies of CKD are scarce in developing countries. This study aims to estimate the cost of illness of all stages of CKD in Lebanon, from early stages until dialysis and kidney transplantation. The secondary objective is to identify factors related to the highest financial burden. METHODS: This is a cross-sectional study of CKD patients who presented to two nephrology clinics during November 2020. Their medical and administrative records were reviewed for collection of demographics, CKD characteristics, direct medical costs (medications, diagnostic tests, hospitalizations, inpatient care, outpatient care), direct non-medical costs (transportation) and indirect costs (productivity losses) for one year. Kruskal Wallis test was used to compare the costs between different CKD stages and categories. Logistic regression analysis was used to evaluate risk factors associated with costs. RESULTS: The sample included 102 non-dialysis CKD patients, 40 hemodialysis, 8 peritoneal dialysis and 10 transplant patients. Their mean age was 66.74 ± 15.36 years, 57.5% were males and 42.5% diabetics. The total median cost per year of CKD across all categories was assessed to be 7,217,500 Lebanese Pounds (3,750,000-35,535,250; 1 $USD = 1515 LBP in 2019) from the societal perspective and 5,685,500 LBP (2,281,750- 32,386,500) from the third-party payer perspective. Statistical analysis showed a higher total cost in hemodialysis (p < 0.001), higher cost of medications in transplant (p < 0.001) and higher cost in technique modality in peritoneal dialysis (p < 0.001). In a sub-analysis of hemodialysis patients, dialysis vintage negatively correlated with total societal cost (r = -0.391, p = 0.013); the regression analysis found diabetes as a risk factor for higher cost (OR = 2.3; 95%CI: 0.638,8.538; p = 0.201). In the subcategory of CKD-ND patients, age correlated with total societal cost (r = 0.323, p = 0.001); diabetes and coronary artery disease were significantly associated with higher total cost (OR = 2.4; 95%CI: 1.083,5.396; p = 0.031; OR = 3.7; 95%CI: 1.535,8.938; p = 0.004). CONCLUSIONS: This cost of illness study showed a high burden of hemodialysis and peritoneal dialysis cost compared to transplant and non-dialysis CKD patients. It revealed a significantly higher cost of medications in transplant patients. Health policies should target interventions that prevent end-stage kidney disease and encourage kidney transplantation.

Factors predictive of anti-spike antibody titers after COVID-19 vaccination in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have a high prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality, but they may have a weak response to coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: This study aimed to evaluate factors predictive of humoral response in HD patients vaccinated against SARS-CoV-2 infection. MATERIAL AND METHODS: This is a 2-center observational study including HD patients who received the BNT162b2 mRNA vaccine followed by serological measurements 20 days and 4 weeks after the 1st and 2nd dose, respectively. Healthy controls were included. Anti-spike antibody was measured using the chemiluminescent immunoassay (CLIA) method. The quantile regression analysis was performed to assess factors associated with anti-spike antibody titers. RESULTS: Seventy-two HD patients and 22 healthy controls were included. Mean age of dialysis patients and controls was 72.5 ±11.5 years and 45.7 ±17.4 years, respectively. In the HD group, median levels of anti-spike antibody were 3 (interquartile range (IQR): 0.5-26) UI/mL and 391 (IQR: 55-1642) UI/mL after the 1st and 2nd dose, respectively, with response rates of 62.5% and 96.7%. The median level of the anti-spike antibody after the 1st dose in previously infected patients was 8571 (IQR: 2586-19147) UI/mL. There was a significant correlation between anti-spike antibody levels after the 2nd dose and age and anti-hepatitis B surface (HBs) antibody and serum albumin levels (Spearman's rho: r = -0.289, p < 0.001; r = 0.357, p = 0.027; r = 0.317; p = 0.026, respectively). The regression analysis showed a significant association of previous infection and anti-Hbs antibody level with anti-spike antibody level after the 1st dose of vaccine (p < 0.001). After a 5-month follow-up, 2 vaccinated patients contracted COVID-19. CONCLUSIONS: This study showed a response rate of 96.7% to 2 doses of BNT162b2 mRNA vaccine in HD patients and 100% to a single dose in previously infected patients. The level of anti-spike antibody can be predicted by age, anti-Hbs antibodies, serum albumin, and previous infection. Despite the immunization of patients, preventive measures should be maintained in all dialysis units.

Erythropoietin in Acute Kidney Injury (EAKI): a pragmatic randomized clinical trial.

BACKGROUND: Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury. METHODS: This is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin < 11 g/dL and acute kidney injury defined as an increase of serum creatinine of ≥ 0.3 mg/dL within 48 h or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n = 67) and the second received standard of care (control; n = 67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis. RESULTS: There was no statistically significant difference in transfusion need (RR = 1.05, 95%CI 0.65,1.68; p = 0.855), in renal recovery full or partial (RR = 0.96, 95%CI 0.81,1.15; p = 0.671), in need for dialysis (RR = 11.00, 95%CI 0.62, 195.08; p = 0.102) or in death (RR = 1.43, 95%CI 0.58,3.53; p = 0.440) between the erythropoietin and the control group. CONCLUSIONS: Erythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).

Where do you live and what do you do? Two questions that might impact your kidney health.

In many cases the social determinants of health need to be assessed through their interaction with environmental factors. This review looks at the impact of physical location and occupation of individuals on their kidney health. It examines the effect of living at high altitude on kidney function and the relationship between extreme cold or hot temperatures and the incidence of kidney injury. It reviews as well the many occupations that have been linked to kidney disease in high-income and low-and-middle-income countries. As a conclusion, this overview proposes preventive recommendations that could be individualized based on weather, altitude, socio-economic level of the country and occupation of the individual.

Occupational Heat Exposure as a Risk Factor for End-Stage Kidney Disease: A Case-Control Study.

OBJECTIVE: More patients are reaching end-stage kidney disease without evident cause. This study aims to explore occupational risk factors associated with hemodialysis. METHODS: A multicenter matched case-control study included dialysis patients and age, sex, and diabetes-matched controls (normal kidney function). Conditional logistic regression analysis assessed occupational factors associated with dialysis. RESULTS: Two hundred thirty eight hemodialysis patients and 238 controls were included. History of occupational heat exposure (odds ratio [OR] = 1.93; 95% confidence interval [CI]: 1.24 to 3.00), working as a cook (OR = 12; 95% CI: 1.56 to 92.29), as construction worker (OR = 10; 95% CI: 1.28 to 78.12) were associated with higher risk of dialysis. These results were significant in men and in those with kidney disease of unknown etiology. CONCLUSIONS: Occupational heat exposure was found to be associated with hemodialysis. This is an important step for future development of preventive strategies in high-risk professions.

The impact of the SARS-CoV-2 pandemic on the mental health of hemodialysis patients in Lebanon.

Hemodialysis is a necessary treatment for end-stage kidney disease patients. It imposes undergoing three sessions of dialysis per week in a specialized center. Amid the SARS-CoV-2 pandemic, precautionary measures were mandatory in all dialysis facilities and may have negatively impacted patients' well-being. This study aimed to uncover the scale of this effect. We performed a cross-sectional study of all patients undergoing chronic hemodialysis in two dialysis units (one urban and another rural). Patients with Alzheimer's disease were excluded. Patients filled a questionnaire including information on socio-demographics, factors related to the dialysis facility, and the impact of the COVID-19 epidemic on their mental health. A total of 72 patients responded. Their median age was 70 (60.79) years. Of them, 68% were males, 71% were married, and 10% were living alone. Following the pandemic, 35% felt more anxious, with a higher incidence of anxiety in the rural unit (p=0.021). Half of them felt very limited in their relationships, and 29% were isolated from their families. In total, 98% of patients were satisfied with the staff support. The imposed preventive measures were perceived as very strict in 27% of the surveyed patients. The majority of the urban group were bothered for not eating during the session, and they felt significantly more stress than the rural group (p=0.001). The SARS-CoV-2 pandemic increased anxiety among hemodialysis patients from a rural setting. Stress was more prevalent in the urban group and most probably related to limitations in eating during sessions. The majority were satisfied with staff support.

Effects of Caffeinated and Decaffeinated Coffee on Hemodialysis-Related Headache (CoffeeHD): A Randomized Multicenter Clinical Trial.

OBJECTIVES: Historically, headache was reported in up to 76% of hemodialysis patients. Some authors suggested that headache resulted from caffeine withdrawal. This study aims to compare the incidence of headache and hypotension between patients drinking regular or decaffeinated coffee during dialysis. METHODS: One-hundred fifty-six patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter study. Patients with atrial fibrillation were excluded. Group A was given 80 mL of regular coffee and group B 80 mL of decaffeinated coffee (placebo) in the middle of the session for 12 consecutive sessions. Ultrafiltration rate was fixed to a maximum of 13 mL/kg/hour. The primary outcome was the incidence of headache during dialysis. RESULTS: A total of 139 patients completed the trial (6.4% vs. 15.4% of withdrawal in Groups A and B, respectively). The number of sessions with headache was not significantly different between Group A and B (33.3% vs. 37.1% respectively, P = .522), nor the number of sessions with hypotension (27% vs. 26% respectively, P = .539). In a subgroup analysis, headache tended to be more frequent in Group B (P = .06) in 2 categories of patients: those with the highest potassium dialysate (K = 2) and the non-hypertensive patients. CONCLUSIONS: Headache occurred in 35% of patients during their chronic hemodialysis sessions. Caffeine intake did not prevent headache occurrence in these patients.