Prevalence, incidence and predictors of renal impairment in persons with HIV receiving protease-inhibitors in rural Tanzania.

OBJECTIVE: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa. METHODS: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models. RESULTS: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78). CONCLUSIONS: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

Longitudinal Outcomes of COVID-19-Associated Collapsing Glomerulopathy and Other Podocytopathies.

BACKGROUND: The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19-associated collapsing glomerulopathy were median age 57 years (range, 35-72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30-412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19-associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.

HCV Seroprevalence among HIV Patients and Associated Comorbidities at One Primary Health Facility in Rwanda.

Hepatitis C virus (HCV) and HIV have emerged as major viral infections within the past two decades, and their coinfection poses a big challenge with a significant impact in terms of morbidity and mortality associated with liver disease and renal failure. The current study aimed at assessing the prevalence of HCV infection and associated comorbidities among HIV patients at one primary health facility in Rwanda. In total, 417 HIV-positive patients were recruited and included in the study from January 1, 2019 up to June 30, 2019. All participants were screened for HCV infection by using the SD Bioline HCV antibody rapid test. In addition, underlying medical conditions were also recorded as comorbidities. Among 417 participants, 52 exhibited HCV-positive results (12.5%). The group of 41- to 50- and 51- to 60-year-olds had higher prevalence of HIV/HCV coinfection than other age-groups with 3.6% and 4.6%, respectively. Furthermore, five underlying medical conditions were found as comorbidities among the study participants. Those with HIV/HCV coinfection showed higher comorbidities than those with mono-infection including liver toxicity, P value 0.005; tuberculosis, P value 0.005; renal failure, P value 0.003; hypertension, P value 0.001; and diabetes mellitus, P value 0.001. The relative risk ratio of having comorbidities in those groups was 4.09. To conclude, the prevalence of HCV/HIV coinfection is high, and there was a statistical significant association of having comorbidities in HIV/HCV-coinfected group compared with the group of HIV mono-infection, which suggests more intervention in this vulnerable group of patients.

Infarto renal en paciente con infección activa por COVID-19 / Renal infarction in a patient with active COVID -19 infection

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Current status of COVID-19 among hemodialysis patients in the East Azerbaijan Province of Iran.

INTRODUCTION: Management of vulnerable patients during the COVID-19 pandemic requires careful precautions. Hemodialysis patients constitute a large group of at-risk patients that not only suffer from a compromised immune system but also are at a higher risk due to frequent admission to healthcare units. Therefore, a better understanding on the pathogenesis and possible risk factors of COVID-19 in hemodialysis patients is of high importance. METHODS: A total of 670 maintained hemodialysis patients from all dialysis units of the East Azerbaijan Province of Iran, including 44 COVID-19 patients were included in the present study. Possible associations between the backgrounds of patients and the incidence of COVID-19 were assessed. Also, hemodialysis patients with COVID-19 were compared to 211 nonhemodialysis COVID-19 patients. FINDINGS: Chronic glomerulonephritis patients and those with blood group A demonstrated a higher incidence of COVID-19. On the other hand, patients with blood group AB+ and those with hypertension etiology of kidney failure demonstrated a lower incidence of COVID-19. Hemodialysis patients with COVID-19 had higher counts of polymorphonuclears (PMNs) in their peripheral blood compared to other COVID-19 patients. DISCUSSION: A better comprehension on the risk factors associated with COVID-19 in hemodialysis patients can improve our understanding on the pathogenesis of COVID-19 in different situations and help the enhancement of current therapeutics for COVID-19 in hemodialysis patients.

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of <30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of <30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74); P < 0.001}, were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P = 0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P = 0.01) than those with an eCrCl of ≥30 ml/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P = 0.283) or early discontinuation due to abnormal liver function tests (LFTs) (0% versus 3.9%; P = 0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30 ml/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. In conclusion, remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl of <30 ml/min compared to patients with an eCrCl of ≥30 ml/min.

Case Report: Paralytic Ileus: A Potential Extrapulmonary Manifestation of Severe COVID-19.

The COVID-19 pandemic has recently spread worldwide, presenting primarily in the form of pneumonia or other respiratory disease. In addition, gastrointestinal manifestations have increasingly been reported as one of the extrapulmonary features of the virus. We report two cases of SARS-CoV-2 infection complicated by paralytic ileus. The first patient was a 33-year-old man who was hospitalized with severe COVID-19 pneumonia requiring ventilator support and intensive care. He developed large bowel dilatation and perforation of the mid-transverse colon, and underwent laparotomy and colonic resection. Histopathology of the resected bowel specimen showed acute inflammation, necrosis, and hemorrhage, supporting a role for COVID-19-induced micro-thrombosis leading to perforation. The second patient was a 33-year-old man who had severe COVID-19 pneumonia, renal failure, and acute pancreatitis. His hospital course was complicated with paralytic ileus, and he improved with conservative management. Both cases were observed to have elevated liver transaminases, which is consistent with other studies. Several authors have postulated that the angiotensin-converting enzyme 2 receptors, the host receptors for COVID-19, that are present on enterocytes in both the small and large bowel might mediate viral entry and resultant inflammation. This is a potential mechanism of paralytic ileus in cases of severe COVID-19 infection. Recognizing paralytic ileus as a possible complication necessitates timely diagnosis and management.

Association between serum Cystatin C and renal injury in patients with chronic hepatitis B.

To explore the association between serum cystatin C (Cys-C) and renal damage in patients with chronic hepatitis B.We retrospectively analyzed the clinical data of 425 patients with chronic hepatitis B virus (HBV) infection. Liver stiffness measured by FibroScan was used to diagnosis liver fibrosis. Cys-C levels were detected via latex-enhanced immunoturbidimetric assay.A total of 425 patients were enrolled. Among them, 217 were patients with CHB with an eGFR > 90 mL/min/1.73 m and 208 with an eGFR ≤90 mL/min/1.73 m. Cys-C levels significantly differed in patients with eGFR > 90 mL/min/1.73 m compared with patients with eGFR ≤90 mL/min/1.73 m (0.81 ±â€Š0.05 vs 1.05 ±â€Š0.06 mg/L, P < .001). Moreover, the Cys-C levels were 0.82 ±â€Š0.04 mg/L in patients without liver fibrosis, 0.98 ±â€Š0.05 mg/L in patients with mild liver fibrosis, 1.05 ±â€Š0.08 mg/L in patients with advanced liver fibrosis, and 1.12 ±â€Š0.07 mg/L in patients with liver cirrhosis (P < .001). Multivariate analyses were conducted to explore the independent factors associated with a decreased eGFR. Multivariate analysis suggested that T2DM (P = .032), liver fibrosis (P = .013), and Cys-C level (P = .035) were the independent factors associated with the decreased eGFR in patients with CHB. While age (P = .020) and Cys-C level (P = .001) were the independent factors associated with the decreased eGFR in patients with CHB-related fibrosis.The fibrosis group had significantly higher Cys-C levels than those without fibrosis. Routine monitoring of Cys-C levels is of positive significance in preventing the development of renal impairment of CHB patients.

Severe Coronavirus disease 2019 pneumonia patients showed signs of aggravated renal impairment.

BACKGROUND: This objective of this study was to identify a sensitive indicator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Samples were collected from 136 patients with Coronavirus disease 2019 (COVID-19) pneumonia admitted to the Shanghai public health clinical center (116 mild, 20 severe). The concentrations of serum urea, Uric Acid (UA), Creatinine (CREA), Erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), and urine protein (Pro) have been tested in this study. RESULTS: Higher levels of urea (female 7.00 ± 3.31, male 8.87 ± 5.18) Pro (female7/7, male 12/13), hs-CRP (female 2/7, male 5/13) ESR (female 94.43 ± 33.26, male 67.85 ± 22.77) were found in severe patients compared with the mild (urea: female 3.71 ± 1.00, male 4.42 ± 1.14; Pro: female 3/46, male 12/70; hs-CRP: female 1/46, male 3/70; ESR: female 43.32 ± 33.24, male 21.64 ± 21.82). UA is lower in the severe group (female 146.90 ± 54.01, male 139.34 ± 66.95) than in mild group (female 251.99 ± 64.35, male 339.81 ± 71.32). CREA and PCT did not show a significant difference between mild and severe patients, but the difference among the five biological markers (urea, Pro, hs-CRP, ESR, and UA) between mild and severe patients we tested was small (P < .05). CONCLUSION: Severe COVID-19 patients had higher levels of urea and Pro, while their UA levels were lower, reflecting poor kidney function in severe patients. However, higher levels of hs-CRP, ESR indicated that inflammatory responses were more active in severe patients.

Pediatric Life-Threatening Coronavirus Disease 2019 With Myocarditis.

We report the case of a pediatric life-threatening coronavirus disease 2019 who presented as myocarditis with heart failure. Clinicians should be aware of this severe presentation of the disease in children, possibly linked to an exaggerated inflammatory host immune response to severe acute respiratory syndrome coronavirus 2.

Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases.

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.

Rabies, rabies vaccine, and renal failure: Clinical issues.

Rabies is an important neurological infection that is prevalent in tropical countries. The rabid animals can bring rabies to humans by biting. The disease can result in serious neurological problem and death is the end result. The best way is prevention of disease by postexposure prophylaxis against rabies. The effect of rabies on the renal system is little mentioned in the literature. In the previous literature, acute kidney injury was observable in half of the rabies patients. Rabies is also transmittable by organ transplantation. Although it is rare and <10 cases had ever been reported in literature, it is proven that kidney transplant patients are at risk of getting rabies if the donor come from endemic country or with a history of travel to endemic country and has unclear cause of death. Regarding rabies immunization, the use of vaccination for patients with the underlying renal failure is interesting. In this short article, the authors summarize on those important clinical issues of rabies and renal failure.

Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.