De novo or recurrent glomerulonephritis and acute tubulointerstitial nephritis after COVID-19 vaccination: A report of six cases from a single center.

Billions of COVID-19 vaccine doses have been administered to combat the ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2. While these vaccines are considered safe, with most adverse events being mild to moderate and transient, uncommon systemic side effects of the vaccines, including de novo or re-activation of various glomerular diseases have recently been observed. We report 6 patients who developed glomerular or acute tubulointerstitial disease shortly after receiving COVID-19 vaccinations. Five of these patients received mRNA vaccines (3 Moderna, 2 Pfizer-BioNTech) and 1 received adenovirus-26 vector vaccine (Johnson and Johnson/Janssen). Four of our patients developed de novo glomerulonephritis or acute tubulointerstitial nephritis (ATIN), while the other 2 had re-activation of prior glomerulonephritis. Two patients presented with acute kidney injury (AKI) characterized by severe ATIN. While both of them also had evidence of immune complex glomerular disease, ATIN was the dominant feature on the biopsies. Two other patients presented with high-grade proteinuria and AKI. Like the aforementioned patients, these patients had evidence of immune complex glomerular disease, but acute onset nephrotic syndrome was the leading clinical feature. Another patient presented with de novo myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-associated pauci-immune crescentic glomerulonephritis. Yet another patient had re-activation of immunoglobulin-A glomerulonephritis that had been quiescent for several years prior to the vaccination. It is difficult to ascertain any causal relationship between COVID-19 vaccination and onset/recurrence of kidney diseases. However, vigilance about occurrence of such complications is imperative. Importantly, all our cases responded well to the immunosuppressive treatment.

Peritoneal Dialysis Use in Patients With Ascites: A Review.

The past few decades have seen steady increase in the prevalence of kidney failure needing kidney replacement therapy. Concomitantly, there has been progressive growth of heart failure and chronic liver disease, and many such patients develop ascites. Therefore, it is not uncommon to encounter patients with kidney failure who concurrently have ascites. The presence of ascites adds many challenges in the management of kidney failure. Poor hemodynamics make volume management difficult. The presence of coagulopathy, malnutrition, and encephalopathy compounds the complexity of the management. Such patients do not tolerate hemodialysis well. However, several concerns have limited the use of peritoneal dialysis (PD), so hemodialysis remains the predominant dialysis modality in these patients. However, observational studies have illustrated that PD provides hemodynamic stability and facilitates better volume management compared with hemodialysis. Moreover, PD obviates the need for therapeutic paracentesis by facilitating continuous drainage of ascites. PD potentially reduces hemorrhagic complications by avoiding routine anticoagulation use. Moreover, small studies have suggested that outcomes such as peritonitis and mechanical complications are comparable to those in PD patients without ascites. PD does not affect transplant candidacy, and these patients can successfully receive combined liver and kidney transplants. Hence, PD should be considered a viable dialysis option in kidney failure patients with ascites.

Physiological principles underlying the kidney targeting of renal nanomedicines.

Kidney disease affects more than 10% of the global population and is associated with considerable morbidity and mortality, highlighting a need for new therapeutic options. Engineered nanoparticles for the treatment of kidney diseases (renal nanomedicines) represent one such option, enabling the delivery of targeted therapeutics to specific regions of the kidney. Although they are underdeveloped compared with nanomedicines for diseases such as cancer, findings from preclinical studies suggest that renal nanomedicines may hold promise. However, the physiological principles that govern the in vivo transport and interactions of renal nanomedicines differ from those of cancer nanomedicines, and thus a comprehensive understanding of these principles is needed to design nanomedicines that effectively and specifically target the kidney while ensuring biosafety in their future clinical translation. Herein, we summarize the current understanding of factors that influence the glomerular filtration, tubular uptake, tubular secretion and extrusion of nanoparticles, including size and charge dependency, and the role of specific transporters and processes such as endocytosis. We also describe how the transport and uptake of nanoparticles is altered by kidney disease and discuss strategic approaches by which nanoparticles may be harnessed for the detection and treatment of a variety of kidney diseases.

Epidemiology Trend of Chronic Kidney Disease in a Semi-Urban Tertiary Hospital in Sub-Saharan Africa.

Background The global burden of chronic kidney disease (CKD) has been on an alarming increase in the last two decades. The morbidity and mortality associated with CKD are even worse in Nigeria, like other developing countries, due to multiple socioeconomic and demographic factors in the country. CKD contributes to the increasing need for hospital admission. Hypertension and chronic glomerulonephritis have been the leading causes of CKD in Nigeria. However, diabetic nephropathy has recently gained more significance as a cause of CKD in developing countries. Aim and methods This study aimed to describe the current trend in the burden and population characteristics of CKD in Southern Nigeria. This is a cross-sectional, hospital-based study. The study recruited adult patients with prehemodialysis CKD seen in renal clinics over a two-year period (November 2014 to October 2016). Data were obtained using a questionnaire and from the clinic register. All participants were clinically assessed, including history, anthropometric measurements, and urinary albumin-creatinine ratio. Results A total of 1,549 patients were seen at the Medical Outpatient Clinic over the study period. CKD accounted for 9.7% of medical outpatient clinic attendance. The mean age of participants was 49±13 years. The leading causes of CKD were diabetes mellitus (32%), chronic glomerulonephritis (30%), and hypertension (22%). Among the participants, CKD stages 3, 4, and 5 were prevalent in 26.7%, 43.3%, and 14.7%, respectively. Conclusion and recommendation CKD is very prevalent among medical clinic patients. Diabetic nephropathy seems to be a more significant cause of CKD than was previously reported. Late presentation of patients to nephrologists remains an obstacle to improving CKD outcome in Nigeria. There is need for more intensive preventive measures and early intervention.

Prevalence and Predictors of Peripheral Vascular Disease Amongst Predialysis Hypertensive Chronic Kidney Disease Patients in Southern Nigeria.

BACKGROUND: Peripheral vascular disease (PVD) is an atherosclerotic disease associated with increased morbidity and mortality among chronic kidney disease (CKD) patients. However, despite the substantial burden of PVD in CKD, local data are lacking. OBJECTIVE: To determine the prevalence and predictors of PVD in predialysis CKD patients. METHOD AND MATERIALS: The study was cross-sectional. One hundred fifty hypertensive CKD patients and age- and sex-matched hypertensive non-CKD subjects were consecutively enrolled at the renal unit of Delta State University Teaching Hospital (DELSUTH), Oghara. Structured questionnaires were used to obtain information on participants' demographic data and health status. PVD was defined by an ankle-brachial index of < 0.9 or > 1.4 in either lower extremity. eGFR was calculated from serum creatinine using the MDRD equation. RESULTS: The mean ages of the study and control groups were 48±14 and 51±15years, respectively. The sex ratio was 3:2 in favour of males for both the study and control groups. The majority of the study group was in CKD stage 4 (44%). The prevalence of PVD was higher among the CKD group compared with controls (24.0% vs. 14.7%). Of the CKD patients with PVD, 11.1% were symptomatic. Predictors of PVD in the study group were eGFR (B=0.010, 95%CI: 0.007-0.013), diastolic BP (B=-0.005, 95%CI: -0.007- -0.002), MAP (B=-0.018, 95%CI: -0.027- -0.008), urinary ACR (B=-0.0036, 95%CI: -0.040- -0.024) and smoking history (p<0.001, OR=14.71). CONCLUSION AND RECOMMENDATION: PVD is common and largely asymptomatic in CKD patients. The predictors of PVD in this study were eGFR, diastolic BP, mean arterial pressure (MAP), urinary albumin to creatinine ratio (ACR), and smoking. A proactive assessment of PVD and early intervention in CKD patients is needed.

Risk Assessment of Pre-dialysis Chronic Kidney Disease (CKD) Patients for Cardiovascular Disease (CVD) in a Tertiary Hospital in Nigeria: A Case-Controlled Cross-Sectional Study.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the chronic kidney disease (CKD) population. CKD patients are more likely to die from CVD before ever reaching end-stage renal disease (ESRD). The study, therefore, seeks to identify the prevalence of risk factors of CVD in CKD patients such as systemic hypertension, anemia, dyslipidemia, hypoalbuminemia, albuminuria, and abnormal calcium/phosphate products. METHODS: The study was a case-control cross-sectional study where one hundred fifty hypertensive CKD patients and age- and sex-matched hypertensive non-CKD subjects were consecutively enrolled at the renal unit of Delta State University Teaching Hospital (DELSUTH), Oghara. RESULTS: The findings of the study revealed the mean ages of cases and controls to be 48.91±11.93 years and 51.0±15.45 years respectively (p-value 0.182). There was an equal number of males and females among the study group and controls (92 males and 58 females) making a male-to-female ratio of 3:2. The prevalence of CVD risk factors such as diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, elevated low-density lipoprotein, anemia, hypocalcemia, hyperphosphatemia, albuminuria, and hypoalbuminemia was significantly higher among the CKD group compared to controls. Similarly, the prevalence of reduced high-density lipoprotein (HDL) was higher among cases than controls, the difference was however not statistically significant. CONCLUSION: The study has shown that systemic hypertension, diabetes, anemia, dyslipidemia, hypoalbuminemia, albuminuria, and abnormal calcium/phosphate products increases the risk for CVD in the general population but is more expressed and significant in CKD patients.

Effect of COVID-19 on Kidney Disease Incidence and Management.

The COVID-19 outbreak has had substantial effects on the incidence and management of kidney diseases, including AKI, ESKD, GN, and kidney transplantation. Initial reports from China suggested a lower AKI incidence in patients with COVID-19, but more recent studies from North America reveal a much higher incidence, likely due to the higher prevalence of comorbid conditions, such as hypertension, diabetes, and CKD. AKI in this setting is associated with worse outcomes, including the requirement for vasopressors or mechanical ventilation and death. Performing RRT in those with AKI poses challenges, such as limiting exposure of staff, preserving PPE, coagulopathy, and hypoxemia due to acute respiratory distress syndrome. Continuous RRT is the preferred modality, with sustained low-efficiency dialysis also an option, both managed without 1:1 hemodialysis nursing support. Regional citrate is the preferred anticoagulation, but systemic unfractionated heparin may be used in patients with coagulopathy. The ultrafiltration rate has to be set carefully, taking into consideration hypotension, hypoxemia, and responsiveness to presser and ventilatory support. The chance of transmission puts in-center chronic hemodialysis and other immunosuppressed patients at particularly increased risk. Limited data show that patients with CKD are also at increased risk for more severe disease, if infected. Little is known about the virus's effects on immunocompromised patients with glomerular diseases and kidney transplants, which introduces challenges for management of immunosuppressant regimens. Although there are no standardized guidelines regarding the management of immunosuppression, several groups recommend stopping the antimetabolite in hospitalized transplant patients and continuing a reduced dose of calcineurin inhibitors. This comprehensive review critically appraises the best available evidence regarding the effect of COVID-19 on the incidence and management of kidney diseases. Where evidence is lacking, current expert opinion and clinical guidelines are reviewed, and knowledge gaps worth investigation are identified.

How To Build a Successful Urgent-Start Peritoneal Dialysis Program.

In-center hemodialysis (HD) remains the predominant dialysis therapy in patients with ESKD. Many patients with ESKD present in late stage, requiring urgent dialysis initiation, and the majority start HD with central venous catheters (CVCs), which are associated with poor outcomes and high cost of care. Peritoneal dialysis (PD) catheters can be safely placed in such patients with late-presenting ESKD, obviating the need for CVCs. PD can begin almost immediately in the recumbent position, using low fill volumes. Such PD initiations, commencing within 2 weeks of the catheter placement, are termed urgent-start PD (USPD). Most patients with an intact peritoneal cavity and stable home situation are eligible for USPD. Although there is a small risk of PD catheter-related mechanical complications, most can be managed conservatively. Moreover, overall outcomes of USPD are comparable to those with planned PD initiations, in contrast to the high rate of catheter-related infections and bacteremia associated with urgent-start HD. The ongoing coronavirus disease 2019 pandemic has further exposed the vulnerability of patients with ESKD getting in-center HD. PD can mitigate the risk of infection by reducing environmental exposure to the virus. Thus, USPD is a safe and cost-effective option for unplanned dialysis initiation in patients with late-presenting ESKD. To develop a successful USPD program, a strong infrastructure with clear pathways is essential. Coordination of care between nephrologists, surgeons or interventionalists, and hospital and PD center staff is imperative so that patient education, home visits, PD catheter placements, and urgent PD initiations are accomplished expeditiously. Implementation of urgent-start PD will help to increase PD use, reduce cost, and improve patient outcomes, and will be a step forward in fostering the goal set by the Advancing American Kidney Health initiative.

Pregnancy and lupus nephritis in developing countries: A systematic review.

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have a significant impact on the course of pregnancy, as well as on maternal and fetal outcomes. LN in pregnancy can increase the maternal risks of SLE flare, acute kidney injury, preeclampsia, and even death. It also affects fetal outcomes by the increased risk of intrauterine growth retardation, premature delivery, and fetal loss. Successful pregnancy outcomes have been well documented in the developed world, but less is known about patients in developing nations. We searched PubMed and Google scholar for all articles published from 1999 to 2016 in developing countries. Twelve of 13 studies were included excluding only one. All studies were independently reviewed. Most of the studies reported a significant association between high flare rates of LN and higher rates of disease flare. Higher rates of active disease at conception were associated with lower live birth rates. Similarly, high flare rates of LN were associated with higher rates of fetal loss. With regard to geographic trends, Indian studies reported lower overall live birth rates and higher rates of active disease at conception. Interestingly, lower rates of preeclampsia were also noted in Indian studies. Higher rates of flare were observed in other Asian studies, but not the Indian studies. Although LN and active SLE at conception are associated with poor fetal outcomes, better outcomes are possible with proper management, even in low-resource settings. More research is necessary to fully understand the relationships between active disease at conception or LN and flare rates, live birth rates, and fetal loss rates in developing countries.

Prevalence and risk factors of intra-dialytic hypotension: a 5 year retrospective report from a single Nigerian Centre.

INTRODUCTION: Intra-dialytic hypotension (IDH) is a common complication of haemodialysis that impacts negatively on the patient's quality of life and can induce serious cardiovascular events. METHODS: Records of all adults who had haemodialysis treatments from Jan 2012-Jan 2016 were reviewed. Socio-demographic data, health status of patient, aetiology of renal disease, clinical and biochemical parameters such as systolic and diastolic blood pressures (SBP and DBP), packed cell volume, were collated using Microsoft Excel. RESULTS: The overall prevalence of intra-dialytic hypotension was 8.6%. Of all haemodialysis patients, 45.7% experienced a drop in SBP > 20mmHg, 28.5% required nurses' intervention and 8.6% had symptoms. Diagnosis of obstructive nephropathy (OR: 3.1, CI:1.43-6.60, p = < 0.004) and sepsis (OR: 3.57, CI: 1.31- 9.75, P = 0.013) increased the odds of experiencing IDH. Only 5% of patients with predialysis SBP < 100mmHg developed IDH (OR: 0.12, CI: 0.02-0.93, P = 0.04). CONCLUSION: IDH was common among the patients studied. It was more prevalent among patients with obstructive nephropathy and sepsis; however other traditional risk factors of IDH such as older age and anaemia, were not found to be significantly associated with IDH. Surprisingly, prevalence of IDH was significantly less among patients with pre-dialysis hypotension compared to those without.

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.

BACKGROUND AND OBJECTIVES: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS: Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS: In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.

Characteristics and Outcomes of Renal Transplant Recipients with Hemolytic Uremic Syndrome in the United States.

BACKGROUND: Hemolytic uremic syndrome (HUS) accounts for <1% of renal transplants in the US. There are limited data on the characteristics and outcomes of HUS in pediatric and adult kidney transplant recipients in the US. METHODS: This study included all renal transplant recipients identified with HUS (N=1,233) as a cause of end-stage renal disease between 1987 and 2013 using the UNOS/OPTN database. The cohort was divided into two age groups: pediatric (N=447) and adult (N=786). Main outcomes were acute rejection rate at one-year, allograft and patient survival, and recurrence of HUS post-transplant. Both age groups were then compared with a propensity score (1:2 ratio) matched control group with an alternative primary kidney disease (non-HUS cohort: pediatric [N= 829] and adult [N=1,547]). RESULTS: In pediatric cohort, when compared to the PS matched controls, acute rejection, death censored allograft and patient survival was similar in the HUS group. However, in the adult cohort, the graft and patient survivals were significantly worse in the HUS group. HUS was associated with allograft loss (HR=1.40, 95%CI 1.14-1.71) in adult recipients. Patients with HUS recurrence had significantly lower allograft and patient survival rates compared to the non-recurrent group in both age groups. Acute rejection was one of the major predictor of HUS recurrence in adults (OR=2.64, 95%CI 1.25-5.60). Calcineurin inhibitors (CNI) were not associated HUS recurrence in both age groups. CONCLUSION: Pediatric HUS-patients, unlike adult recipients, have similar outcomes compared to the PS matched controls. Recurrence of HUS is associated with poor allograft and patient survival in pediatric and adult patients. Use of CNIs seem to be safe as a part of maintenance immunosuppression post-transplantation. A comprehensive national registry is urgently needed.

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.

BACKGROUND AND OBJECTIVES: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. RESULTS: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. CONCLUSIONS: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

A Case of Alport Syndrome with Posttransplant Antiglomerular Basement Membrane Disease despite Negative Antiglomerular Basement Membrane Antibodies by EIA Treated with Plasmapheresis and Intravenous Immunoglobulin.

Posttransplant antiglomerular basement membrane (anti-GBM) disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA). On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG.