Renin-angiotensin system activation: may it increase frequency of obstructive sleep apnea in patients with autosomal dominant polycystic kidney disease?

PURPOSE: Renin-angiotensin system (RAS) hyperactivity is a common entity in both autosomal dominant polycystic kidney disease (ADPKD) and obstructive sleep apnea (OSA). We aimed to investigate the frequency of OSA in adults with ADPKD either with stages 3-4 or stages 1-2 chronic kidney disease (CKD) and evaluate the effect of RAS blockade on OSA in these patients. METHODS: This is a comparative, prospective, two-center clinical study. Eligible patients with ADPKD were enrolled in a polysomnography (PSG) study. Presence of OSA in patients with ADPKD was compared with individuals who underwent polisomnography study due to OSA symptoms. A subgroup analysis was performed in terms of the presence of OSA in ADPKD with eGFR values lower or higher than 60 ml/min/1.73 m2 (stages 3-4 and stages 1-2 CKD, respectively). RESULTS: Frequency of OSA (65%) was higher than in the general population and similar between the two groups (p = 0.367). Patients with ADPKD and eGFR ≥ 60 ml/min/1.73 m2 presented a similar frequency of OSA to the control group (p = 0.759). However, OSA was significantly more frequent in ADPKD with eGFR < 60 ml/min/1.73 m2 (p = 0.018). Subgroup analysis revealed that presence of OSA also was significantly higher in ADPKD with lower eGFR levels (eGFR < 60 ml/min/1.73 m2 and eGFR > 60 ml/min/1.73 m2) 14/17 (82%) and 12/23 (52%), respectively (p: 0.048). CONCLUSION: As kidney disease progresses, uremia and related factors of renal failure rather than RAS activation seem to play a more important role for the development of OSA in patients with ADPKD.

COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic.

BACKGROUND: Kidney transplant recipients have an increased risk of complications from COVID-19. However, data on the risk of allograft damage or death in kidney transplant recipients recovering from COVID-19 is limited. In addition, the first and second waves of the pandemic occurred at different times all over the world. In Turkey, the Health Minister confirmed the first case in March 2020; after that, the first wave occurred between March and August 2020; afterward, the second wave began in September 2020. This study aims to demonstrate the clinical presentations of kidney transplant recipients in the first two waves of the pandemic in Turkey and explore the impact of COVID-19 on clinical outcomes after the initial episode. METHODS: Patients with COVID-19 from seven centers were included in this retrospective cohort study. Initially, four hundred and eighty-eight kidney transplant recipients diagnosed with COVID-19 between 1 March 2020 to 28 February 2021 were enrolled. The endpoints were the occurrence of all-cause mortality, acute kidney injury, cytokine storm, and acute respiratory distress syndrome. In addition, longer-term outcomes such as mortality, need for dialysis, and allograft function of the surviving patients was analyzed. RESULTS: Four hundred seventy-five patients were followed up for a median of 132 days after COVID-19. Forty-seven patients (9.9%) died after a median length of hospitalization of 15 days. Although the mortality rate (10.1% vs. 9.8%) and intensive care unit admission (14.5% vs. 14.5%) were similar in the first two waves, hospitalization (68.8% vs. 29.7%; p < 0.001), acute kidney injury (44.2% vs. 31.8%; p = 0.009), acute respiratory distress syndrome (18.8% vs. 16%; p = 0.456), and cytokine storm rate (15.9% vs. 10.1%; p = 0.072) were higher in first wave compared to the second wave. These 47 patients died within the first month of COVID-19. Six (1.4%) of the surviving patients lost allografts during treatment. There was no difference in the median serum creatinine clearance of the surviving patients at baseline (52 mL/min [IQR, 47-66]), first- (56 mL/min [IQR, 51-68]), third- (51 mL/min [IQR,48-67]) and sixth-months (52 mL/min [IQR, 48-81]). Development of cytokine storm and posttransplant diabetes mellitus were independent predictors for mortality. CONCLUSIONS: Mortality remains a problem in COVID-19. All the deaths occur in the first month of COVID-19. Also, acute kidney injury is common in hospitalized patients, and some of the patients suffer from graft loss after the initial episode.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

PURPOSE: Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. METHODS: Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. RESULTS: Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). CONCLUSION: As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

Uric acid as a prognostic predictor in COVID-19.

Objective: The purpose of our study was to investigate the incidence and prognostic significance of baseline and control uric acid values in COVID-19. Methods: The study population included patients admitted with the diagnosis of SARS-CoV-2 between March 2020 and March 2021. The demographic data, clinical, laboratory, and radiological findings were recorded. Uric acid levels were measured at the time of admission for 498 patients and at the most severe period of the disease in 143 patients. Length of hospital stay, need for admission to intensive care unit, the course, and outcomes during hospitalization were recorded. Results: The mean age of 261 male and 207 female patients was 62.7(21-95) years. At the time of admission, 21 patients had hypouricemia and 170 had hyperuricemia. The need for ICU was 47.6% in the hypouricemic, 19.2% in the normouricemic, and 21.2% in the hyperuricemic groups. The mean uric acid level was 5.24±2.54 mg/dl in patients who required ICU admission and 5.18±1.98 mg/dl in patients who were discharged from the ward. The difference was not statistically significant. The mean uric acid level was not significantly different in the deceased and survivors. In 143 subjects, uric acid levels were measured after the progression of COVID-19; 73 of them were admitted to the ICU. The mean uric acid levels were found to be significantly decreased in patients with a negative prognosis. Conclusion: In our study, hypouricemia was not found to be a major feature of SARS-CoV-2 infection. Low baseline uric acid levels were associated with increased ICU admission. The decline in uric acid levels during hospital stay predicted poor prognosis, as well.

Medium Cut-Off Dialysis Membranes: Can They Have Impact on Outcome of COVID-19 Hemodialysis Patients?

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may lead to high levels of expression of inflammatory cytokines. Medium cut-off (MCO) membranes may make greater clearances for large-middle molecules (including cytokines) than low-flux (LF) membranes. In this study, we aimed to evaluate the impact of MCO membranes on outcome of COVID-19 patients on hemodialysis (HD). METHODS: Sixty COVID-19 HD patients were included in this study. The patients were categorized into 2 groups regarding type of HD membranes. Clinical data were taken from medical records. RESULTS: Initial crp and ferritin levels, which are surragates of cytokine storm and severity of disease in COVID-19, were significantly higher in MCO membrane group compared to LF group (p = 0.037 and 0.000, respectively). Although there were more patients with severe disease in MCO group, there were no significant differences regarding need for intensive care unit and death. CONCLUSION: It may be an option to use MCO membranes in HD patients with COVID-19 in order to reduce cytokine levels and prevent cytokine storm.

COVID-19 in kidney transplant recipients: A multicenter experience in Istanbul.

INTRODUCTION: Management of COVID-19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID-19. MATERIAL AND METHODS: Kidney transplant recipients diagnosed with COVID-19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all-cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation. RESULTS: Forty patients were reviewed retrospectively over a follow-up period of 32 days after being diagnosed with COVID-19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow-up in the intensive care unit. None of the patients developed graft loss during follow-up. DISCUSSION: COVID-19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte-depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.

A randomized study to assess the efficacy of herbal product to prevent cisplatin-induced nephrotoxicity in a rat model.

OBJECTIVES: This study aimed to investigate the protective effect and antioxidant activity of an herbal product that made from multiple plants in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. MATERIALS AND METHODS: Twenty-four rats were divided into four different groups namely: Group 1 - control healthy animals without any specific medication, Group 2 - Herbal product only 5 mg/kg, Group 3 - cisplatin only and Group 4 - Herbal product 5 mg/kg + cisplatin. RESULTS: Evaluation of our findings demonstrated a significant (p = 0.017) reduction in Catalase activities and a significant increase (p = 0.001) in renal tissue Malondialdehyde levels in cisplatin- treated rats when compared with the control group. Also, Glutathion and Glutathione peroxidase content revealed significant (p = 0.031) reduction in renal tissues of cisplatintreated rats compared with the control group. Pre-treatment of rats with the herbal product ameliorated these cisplatininduced changes of the antioxidant enzymes. No statistically significant changes were demonstrated in Superoxide dismutase activities in the tissue specimens of any group. CONCLUSIONS: This potent antioxidant herbal medicine was found to have potential antioxidant activity, which may in turn to be effective in the protection of kidney tissue resulting from cisplatin application. Therefore, much attention should be given to the possible role of natural dietary antioxidants for protecting the kidney.

Arteriovenous fistula as the vascular access contributes to better survival of hemodialysis patients with COVID-19 infection.

BACKGROUND: While COVID-19 in chronic hemodialysis patients has high mortality and the pandemic will not end in the near future, effective follow up strategies should be implemented for these patients. Surgeries have been triaged according to their level of urgencies and arteriovenous fistula (AVF) operations were among elective surgeries. This study aimed to analyze the effect of vascular access on the outcomes of hemodialysis patients who had COVID-19. METHODS: One hundred four hemodialysis patients who had COVID-19 were retrospectively analyzed. Seventy-two of them had AVF as the vascular access while 32 of them had tunneled catheters. Inflammatory markers and outcomes of patients with AVFs and catheters were compared. A logistic regression analysis was performed in order to define factors that contribute to better outcomes in hemodialysis patients. RESULTS: COVID-19 had high mortality rate in hemodialysis patients (36.5%). Patients with catheters have higher peak ferritin levels (p = 0.02) and longer hospital stay (p = 0.00). Having AVF as the vascular access (OR = 3.36; 95% CI: 1.05-10.72; p = 0.041) and using medium cut-off dialyzers (OR = 7.99; 95% CI: 1.53-41.65; p = 0.014) were related to higher survival of the patients. COVID severity was inversely proportional to the survival (p = 0.000). CONCLUSIONS: AVFs contribute to higher survival of hemodialysis patients with COVID-19. Even in the pandemic era, end stage renal disease patients should be given the opportunity to have their vascular access properly created.

Are thiazides effective on hypertensive vertigo? A preliminary study.

OBJECTIVES: In this study, we aimed to investigate whether the symptoms of vertigo related to hypertension resulted from endolymphatic hydrops and the efficacy of the thiazides in the treatment. PATIENTS AND METHODS: A total of 24 vertigo patients without peripheric or central vestibular pathologies or hyperlipidemia were included. The study group comprised 15 patients with hypertension, including nine with regulated non-insulin-dependent diabetes mellitus (DM). The control group comprised nine patients without hypertension or DM. The patients in the study group received hydrochlorothiazide treatment. The European Evaluation of Vertigo Scale (EEVS) and Vertigo Handicap Questionnaire (VHQ), puretone audiometry, tympanometry, electronystagmography (ENG) for nystagmus tests, oculomotor tests, and caloric test were carried out initially and at three weeks for both groups. The results of the study group were compared to those of the control group. RESULTS: There was a statistically significant decrease in the scores of EEVS and VHQ at three weeks in the study group, compared to the baseline scores (for both groups p≤0.01). CONCLUSION: Our study results showed that thiazides alleviated vertigo symptoms in hypertensive patients, as measured by qualitative methods (i.e. EEVS, VHQ), but not with quantitative measurements (i.e. ENG).

Waning of SARS-CoV-2 Vaccine-Induced Immune Response over 6 Months in Peritoneal Dialysis Patients and the Role of a Booster Dose in Maintaining Seropositivity.

INTRODUCTION: Although lower than general population, newly developed SARS-CoV-2 vaccines generate immune responses in end-stage kidney disease patients. However, the persistence of immune responses in the long term is not known yet. This study aimed to evaluate humoral immune responses in peritoneal dialysis (PD) patients over 6 months and to analyze the effects of the booster dose. METHODS: Humoral immune responses of PD patients were measured after initial SARS-CoV-2 vaccinations and after 6 months following initial vaccinations. Immune responses were compared between patients who received and did not receive booster doses. PD patients were compared with 41 hemodialysis (HD) patients and 61 healthy controls. Humoral immune responses were measured by a commercial test that detects antibodies toward the receptor-binding domain of the spike protein of SARS-CoV-2. RESULTS: Twenty PD patients were evaluated over 6 months. The initial seropositivity rate was 90.9% with inactivated vaccine and 100% with mRNA vaccine. Seropositivity decreased to 44.4% after 6 months, and a booster dose helped in maintaining the 100% of seropositivity (p = 0.005). Magnitude of humoral response at the 6th month was also higher in patients who received the third dose (1,132.8 ± 769.6 AU/mL vs. 400.0 ± 294.6 AU/mL; p = 0.015). Among patients who did not receive the third dose, those who got mRNA vaccine could maintain higher seropositivity than others who got inactivated vaccine (75% vs. 40% for PD, 81.8% vs. 50% for HD). Seropositivity and antibody levels were similar for PD and HD patients after 6 months (p = 0.24 and 0.56) but lower than healthy controls (p = 0.0013). CONCLUSION: SARS-CoV-2 vaccine-induced antibody levels and seropositivity of PD patients significantly fall after 6 months. A booster dose after around 3 months following initial immunization might help in maintaining seropositivity.

Surveillance of hemodialysis related infections: a prospective multicenter study.

As in many countries, there is neither a surveillance system nor a study to reveal the hemodialysis (HD) related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC's surveillance system. A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network (NHSN) dialysis event (DE) protocol is adopted for definitions and reporting. During April 2016-April 2018, 9 centers reported data. A total of 199 DEs reported in 10,035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). This first surveillance study revealed the baseline status of HD related infections in Turkey and showed that CDC National Healthcare Safety Network (NHSN) DE surveillance system can be easily implemented even in a high workload dialysis unit and be adopted as a nationwide DE surveillance program.

COVID-19 in chronic kidney disease: a retrospective, propensity score-matched cohort study.

BACKGROUND: The prognostic factors for COVID-19 in patients with chronic kidney disease (CKD) are uncertain. We conducted a study to compare clinical and prognostic features between hospitalized COVID-19 patients with and without CKD. METHODS: Fifty-six patients with stage 3-5 CKD and propensity score-matched fifty-six patients without CKD were included in the study. Patients were followed-up at least fifteen days or until death after COVID-19 diagnosis. The endpoints were death from all causes, development of acute kidney injury (AKI) or cytokine release syndrome or respiratory failure, or admission to the intensive care unit (ICU). RESULTS: All patients were reviewed retrospectively over a median follow-up of 44 days (IQR, 36-52) after diagnosis of COVID-19. Patients with CKD had higher intensive care unit admission and mortality rates than the patients without CKD, but these results did not reach statistical significance (16 vs. 19; p = 0.54 and 11 vs. 16, p = 0.269, respectively). The frequency of AKI development was significantly higher in predialysis patients with CKD compared to the other group (8 vs. 5; p < 0.001), but there was no significant difference between the groups in terms of cytokine release syndrome (13 vs. 8; p = 0.226), follow-up in the ICU (19 vs. 16; p = 0.541), and respiratory failure (25 vs. 22, p = 0.566). Multivariate logistic regression analysis revealed that respiratory failure and AKI were independent risk factors for mortality. CONCLUSION: The mortality rates of COVID-19 patients with CKD had higher than COVID-19 patients without CKD. Also, AKI and respiratory failure were independently related to mortality.

Reversibility of microalbuminuria with continuous positive airway pressure treatment in obstructive sleep apnea syndrome.

INTRODUCTION: Microalbuminuria is an early marker of kidney damage and an early predictor and risk factor for cardiovascular diseases. We aimed to evaluate the association between albuminuria levels in different severity obstructive sleep apnea syndrome (OSAS) cases and to find out the efficacy of CPAP treatment on microalbuminuria. MATERIALS AND METHODS: We conducted a prospective study on subjects who underwent polysomnography. The polysomnographic data were recorded to establish the presence and severity of OSAS. The blood and urine samples were taken both at the time of diagnosis and 3 months after CPAP therapy. The relationship between the severity of OSAS and microalbuminuria and the effect of CPAP treatment on microalbuminuria were evaluated. RESULTS: The study population consisted of 449 subjects. Better compliance to CPAP was associated with significantly reduced levels of microlbuminuria. Urinary albumin/creatinine was increased in severe cases, but the difference was not statistically significant. In the non-compliant group, microalbumin/creatinine ratio was 25.24 prior to initiation of CPAP treatment and 28.36 at the third month control visit (p = 0.25). In the compliant group, microalbumin/creatinine ratio was 49.71 prior to initiation of CPAP treatment and 22.30 at the third month control visit (p = 0.04). CONCLUSION: Our study demonstrated that good compliance to CPAP therapy is associated with a decrease in microalbuminuria. Patients who used CPAP regularly had a significant decline in albumin/creatinine ratio after 3 months of CPAP therapy.

The clinical characteristics and course of COVID-19 in hemodialysis patients.

INTRODUCTION: In December 2019, pneumonia cases emerging in China rapidly spread and became a global pandemic. The disease called COVID-19 threatens health and life in patients with comorbid disease, especially in patients with kidney failure. In this study, we aimed to evaluate the clinical findings, laboratory parameters, and prognosis of COVID-19 disease in end-stage renal patients undergoing hemodialysis treatment. METHODS: We included the hemodialysis patients who have been diagnosed with COVID-19 disease and received inpatient treatment between 11 Match 2020 and 24 April 2020 in hospital. The demographic characteristics, comorbidities, symptoms, clinical course, laboratory parameters, and treatments were recorded. FINDINGS: The study included 25 hemodialysis patients; 15 (60%) were female. The mean age was 60.5 ± 15 years. All patients had chest computed tomography findings compatible with COVID-19 disease. The findings were bilateral in 88% of patients. The real-time reverse transcriptase-polymerase chain reaction test was positive in 48% of the patients. The most common symptoms were dyspnea (56%) and fever (52%). The most common comorbid disease was hypertension (76%). Leukocytosis in 12% of the patients while 72% had lymphopenia. All patients had a high C-reactive protein value. 64% of patients required oxygen support and 32% intensive care. 28% developed a secondary infection. 76% (19/25) of the patients has been discharged with cure and 20% (5/25) died. The inpatient follow-up of a patient (4%) continues. Secondary infection development was significantly associated with oxygen demand (P = 0.027) and need for intensive care (P = 0.001). DISCUSSION: The associated clinical symptoms of COVID-19 were similar in hemodialysis patients to those of patients without renal disease. However, it caused pneumonia in all hemodialysis patients. It was associated with a more severe disease and worse prognosis with a mortality rate of 20%. Our study suggests that COVID-19 disease has a significantly more severe course and worse prognosis in hemodialysis patients.

Peripheral arterial disease diagnosed by ankle-brachial index: Predictor for early renal replacement therapy in chronic kidney disease.

Our study aimed to investigate the relationship between ankle-brachial index (ABI) and need for early renal replacement therapy (RRT) in predialysis patients with chronic kidney disease (CKD). A total of 112 patients (62% men) with pre-dialysis CKD, seen in the outpatient clinic, were included, and ABI was obtained as per standard protocol. Peripheral arterial disease (PAD) was defined as ABI <0.9 or >1.3 in either leg. The clinical data were analyzed, and the risk factors for early RRT were determined by multivariate logistic regression analysis. The prevalence of PAD was 44% in predialysis CKD patients. Over three years' follow- up, 14.2% required RRT; 11.3% developed major cardiovascular event (myocardial infarction, stroke, or death). A total of 26 events occurred. The incidence of all events was significantly higher in patients with abnormal ABI than in those with normal ABI (34.7% vs. 12.7%; log rank P = 0.02). PAD was associated with all events [hazard ratio (HR): 2.72; 95% CI: 1.04-7.17; P = 0.042] as also the need for RRT (HR 3.2; 95% Cl: 1.005-10.23; P = 0.049), on univariate cox proportional hazard analysis. Multivariate logistic regression analysis adjusted for other risk factors identified that PAD remained an independent predictor for the need for early RRT (HR: 12.2; 95%Cl: 2.2-66.5; P = 0.004) and all events (HR: 3.5; 95% Cl: 0.9-13.5; P = 0.032). PAD was an independent predictor for RRT requirement in predialysis CKD.