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Chronic kidney disease (CKD) is one of the most frequent complications associated with type 2 diabetes mellitus (T2DM) and is also an independent risk factor for cardiovascular disease. The mineralocorticoid receptor (MR) is a nuclear receptor expressed in many tissue types, including kidney and heart. Aberrant and long-term activation of MR by aldosterone in patients with T2DM triggers detrimental effects (eg, inflammation and fibrosis) in these tissues. The suppression of aldosterone at the early stage of T2DM has been a therapeutic strategy for patients with T2DM-associated CKD. Although patients have been treated with renin-angiotensin system (RAS) blockers for decades, RAS blockers alone are not sufficient to prevent CKD progression. Steroidal MR antagonists (MRAs) have been used in combination with RAS blockers; however, undesired adverse effects have restricted their usage, prompting the development of nonsteroidal MRAs with better target specificity and safety profiles. Recently conducted studies, Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), have reported that finerenone, a nonsteroidal MRA, improves both renal and cardiovascular outcomes compared with placebo. In this article, we review the history of MRA development and discuss the possibility of its combination with other treatment options, such as sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and potassium binders for patients with T2DM-associated CKD.

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Objectives: The study objectives were to describe the incidence, risk factors, and outcomes of acute kidney injury after cardiopulmonary bypass in Jamaica. Method: We performed a review of the medical records of adult patients (aged ≥ 18 years) with no prior dialysis requirement undergoing cardiopulmonary bypass at the University Hospital of the West Indies, Mona, between January 1, 2016, and June 30, 2019. Demographic, preoperative, intraoperative, and postoperative data were abstracted. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes criteria. The primary outcomes were acute kidney injury incidence and all-cause 30-day mortality. Multivariable logistic regression and Cox proportional analyses were used to examine the association between the acute kidney injury risk factors and the primary outcome. Results: Data for 210 patients (58% men, mean age 58.1 ± 12.9 years) were analyzed. Acute kidney injury occurred in 80 patients (38.1%), 44% with Kidney Disease Improving Global Outcomes I, 33% with Kidney Disease Improving Global Outcomes II, and 24% with Kidney Disease Improving Global Outcomes III. From multivariable logistic regression models, European System for Cardiac Operative Risk Evaluation II (odds ratio, 1.19; 95% confidence interval, 1.01-1.39 per unit), bypass time (odds ratio, 1.94; 95% confidence interval, 1.40-2.67 per hour), perioperative red cell transfusion (odds ratio, 3.03; 95% confidence interval, 1.36-6.76), and postoperative neutrophil lymphocyte ratio (odds ratio, 1.65; 95% confidence interval, 1.01-2.68 per 10-unit difference) were positively associated with acute kidney injury. Acute kidney injury resulted in greater median hospital stay (18 vs 11 days, P < .001) and intensive care unit stay (5 vs 3 days, P < .001), and an 8-fold increase in 30-day mortality (hazard ratio, 8.15; 95% confidence interval, 2.76-24.06, P < .001). Conclusions: Acute kidney injury after cardiopulmonary bypass surgery occurs frequently in Jamaica and results in poor short-term outcomes. Further studies coupled with quality interventions to reduce the mortality of those with acute kidney injury are needed in the Caribbean.

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Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

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Primary membranous nephropathy (pMN) is an auto-immune disease characterized by auto-antibodies targeting podocyte antigens resulting in activation of complement and damage to the glomerular basement membrane. pMN is the most common cause of nephrotic syndrome in adults without diabetes. Despite a very heterogeneous course of the disease, the treatment of pMN has for many years been based on uniform management of all patients regardless of the severity of the disease. The identification of prognostic markers has radically changed the vision of pMN and allowed KDIGO guidelines to evolve in 2021 towards a more personalized management based on the assessment of the risk of progressive loss of kidney function. The recognition of pMN as an antibody-mediated autoimmune disease has rationalized the use immunosuppressive drugs such as rituximab. Rituximab is now a first line immunosuppressive therapy for patients with pMN with proven safety and efficacy achieving remission in 60-80% of patients. For the remaining 20-40% of patients, several mechanisms may explain rituximab resistance: (i) decreased rituximab bioavailability; (ii) immunization against rituximab; and (iii) chronic glomerular damage. The treatment of patients with rituximab-refractory pMN remains controversial and challenging. In this review, we provide an overview of recent advances in the management of pMN (according to the KDIGO 2021 guidelines), in the understanding of the pathophysiology of rituximab resistance, and in the management of rituximab-refractory pMN. We propose a treatment decision aid based on immunomonitoring to identify failures related to underdosing or immunization against rituximab to overcome treatment resistance.

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OBJECTIVES: Acute kidney injury is a common complication after pericardiectomy for constrictive pericarditis, which predisposes patients to worse outcomes and high medical costs. We aimed to investigate potential risk factors and consequences and establish a prediction model. METHODS: We selected patients with constrictive pericarditis receiving isolated pericardiectomy from January 2013 to January 2021. Patients receiving concomittant surgery or repeat percardiectomy, as well as end-stage of renal disease were excluded. Acute kidney injury was diagnosed and classified according to the KDIGO criteria. Clinical features were compared between patients with and without postoperative acute kidney injury. A prediction model was established based on multivariable regression analysis. RESULTS: Among two hundred and eleven patients, ninety-five (45.0%) developed postoperative acute kidney injury, with fourty-three (45.3%), twenty-eight (29.5%), and twenty-four (25.3%) in mild, moderate and severe stages, respectively. Twenty-nine (13.7%) patients received hemofiltration. Nine (4.3%) patients died perioperatively and were all in the acute kidney injury (9.5%) group. Eleven (5.2%) patients were considered to have chronic renal dysfunction states at the 6-month postoperative follow-up, and eight (72.7%) of them experienced moderate to severe stages of postoperative acute kidney injury. Univariable analysis showed that patients with acute kidney injury were older (difference 8 years, P < 0.001); had higher body mass index (difference 1.68 kg·m-2, P = 0.002); rates of smoking (OR = 2, P = 0.020), hypertension (OR = 2.83, P = 0.004), and renal dysfunction (OR = 3.58, P = 0.002); higher central venous pressure (difference 3 cm H2O, P < 0.001); and lower cardiac index (difference -0.23 L·min-1·m-2, P < 0.001) than patients without acute kidney injury. Multivariable regression analysis showed that advanced age (OR 1.03, P = 0.003), high body mass index (OR 1.10, P = 0.024), preoperative atrial arrhythmia (OR 3.12, P = 0.041), renal dysfunction (OR 2.70 P = 0.043), high central venous pressure (OR 1.12, P = 0.002), and low cardiac index (OR 0.36, P = 0.009) were associated with a high risk of postoperative acute kidney injury. A nomogram was established based on the regression results. The model showed good model fitness (Hosmer-Lemeshow test P = 0.881), with an area under the curve value of 0.78 (95% CI: 0.71, 0.84, P < 0.001). CONCLUSION: The prediction model may help with early recognition, management, and reduction of acute kidney injury after pericardiectomy.

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BACKGROUND: Acute Kidney Injury (AKI) is a major and under-recognised cause of morbidity and mortality worldwide. Low and middle-income countries bear the greatest burden of AKI (85%). There is currently no published literature on AKI from the Pacific Islands. The aim of the present study was to report the incidence, aetiology, management and outcomes measures of AKI from the tertiary referral hospital of Samoa. MATERIALS AND METHODS: Single-centre prospective observational study. Participants were recruited by the lead investigator from the hospital patient information system. The inclusion criteria for participation was (1) adults (>18 years) admitted to general wards of Tupua Tamasese Meaole (TTM) Hospital with a diagnosis of AKI between December 1, 2019 and May 31, 2020, and (2) serum creatinine level of >200 µmol/L, and (3) compliance with the current Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI diagnosis. The data collection form was adapted from the International Society for Nephrology - Global Snapshot Project, and recorded demographic and baseline characteristics, precipitating causes of AKI, treatment/management, and outcomes measures. RESULTS: There was a total of 114 AKI admissions over the study period corresponding to a hospital-based AKI incidence of 26.8 per 1000 admissions per 6 months. 75% of AKI cases were community acquired. The leading causes of AKI were dehydration (79%) and sepsis (64%). More than 40% of cases presented with two or more Non-Communicable Disease co-morbidities. The in-patient mortality rate was 20.2%. In the 3 months following discharge from hospital, 25% of AKI cases had completely resolved, 25% of patients had died, and 18.7% of AKI cases had progressed to chronic kidney disease. The leading causes of mortality were cardiovascular events (35%) and sepsis (35%). CONCLUSIONS: The hospital-based incidence and unfavourable outcomes of AKI are high in Samoa. Greater awareness of this under-recognised condition is warranted among the public, government officers, and health professionals.

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Skeletal changes are a common complication in patients with chronic kidney disease and traditionally labelled as renal osteodystrophy. Uremic leontiasis ossea is a rare and severe form of renal osteodystrophy with characteristic overgrowth of the craniofacial bones. Imaging, in particular computed tomography, is valuable for the diagnosis and management of such rare condition. Uremic leontiasis ossea has distinctive imaging features with significant overgrowth of the jaw and characteristic internal serpiginous tunneling. The recognition of its radiological appearance and abrupt management are essential to avoid its devastating esthetic and functional impairments.

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Crossed fused renal ectopia (CFRE) is a rare congenital renal abnormality. It is usually diagnosed incidentally by imaging. Herein we report a 53-year-old patient with renal cell carcinoma of CFRE. He was successfully treated with an open partial nephrectomy and was discharged without any complications. Furthermore, we review similar cases of CFRE to identify the clinical features and surgical technique.

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BACKGROUND: Despite a significant shortage of kidneys for transplantation in the US, kidneys from older deceased donors are infrequently transplanted. This is primarily over concern of graft quality and transplant durability. METHODS: The US national transplant database (2000-2018) was assessed for deceased donor kidney transplant patient and graft survival, graft durability and stratified by donor age (<65 years>), Kidney Donor Profile Index (KDPI) and estimated glomerual filtration rate (GFR) one year post-transplantation (eGFR-1) were calculated. FINDINGS: Recipients of kidneys transplanted from deceased donors >65 years had a lower eGFR-1, (median 39 ml/min) than recipients of younger donor kidneys (median 54 ml/min). However, death-censored graft survival, stratified by eGFR-1, demonstrated similar survival, irrespective of donor age or KDPI. The durability of kidney survival decreases as the achieved eGFR-1 declines. KDPI has a poor association with eGFR-1 and lesser for graft durability. While recipients of kidneys > 65 years had a higher one year mortality than younger kidney recipients, recipients of kidneys > 65 years and an eGFR-1 <30 ml/min, had a lower survival than an untransplanted waitlist cohort (p<0.001). INTERPRETATION: The durability of kidney graft survival after transplantation was associated with the amount of kidney function gained through the transplant (eGFR-1) and the rate of graft loss (return to dialysis) was not significantly associated with donor age. 24.9% of recipients of older donor kidneys failed to achieve sufficient eGFR-1 providing a transplant survival benefit. While there is significant benefit from transplanting older kidneys, better decision-making tools are required to avoid transplanting kidneys that provide insufficient renal function. FUNDING: None.

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INTRODUCTION: India is witnessing high hepatitis C virus (HCV) infection burden in patients of chronic kidney disease. Due to unavailability of costly Kidney Disease Improving Global Outcomes-recommended directly acting antiviral drugs, a widely available pan-genotypic combination of Sofosbuvir and Velpatasvir can become an economical option. Data regarding treatment experience of sofosbuvir-velpatasvir combination in chronic kidney disease is scarce. No data from India have been published in patients on renal replacement therapies till now. METHODS: This retrospective analysis included all patients of end-stage renal disease on maintenance hemodialysis with treatment-naïve chronic HCV infection treated with sofosbuvir (400 mg) and velpatasvir (100 mg) fixed-dose combination. Pretreatment routine investigations were performed, which included HCV viral load, genotype, fibro scan, endoscopy for esophageal varices, and portal vein Doppler. The patients were followed up with HCV viral load to declare sustained virologic response. RESULT: patients were included with a mean age of 39.8 ± 10.8 years, and 77.4% were male. Genotype 1 was found to be most prevalent (67.7%), with a median viral load of 106copies/ml. Six (19.3%) patients had hepatitis B virus co-infection. Three (9.7%) patients had cirrhosis. Sustained virologic response (SVR12) was achieved in 30 (96.8%) patients, and one (3.2%) patient had relapse. Furthermore, 14 (45.2%) patients underwent renal transplantation, and none of them had relapsed. Dyspepsia (9.7%) was the most common side effect observed with no major adverse effect. CONCLUSION: Our study showed excellent efficacy with the safety profile of this drug combination in end-stage renal disease patients. However, larger prospective studies and multicenter randomized controlled trials are needed for further confirmation.

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Acute kidney injury, especially early-stage disease, is a common hospital comorbidity requiring timely recognition and treatment. We investigated the effect of daily laboratory alerting of patients at risk for acute kidney injury as measured by documented International Classification of Diseases diagnoses. A quasi-experimental study was conducted at 8 New York hospitals between January 1, 2014, and June 30, 2017. Education of clinical documentation improvement specialists, physicians, and nurses was conducted from July 1, 2014, to December 31, 2014, prior to initiating daily hospital-wide laboratory acute kidney injury alerting on January 1, 2015. Incidence based on documented International Classification of Diseases diagnosis of acute kidney injury and acute tubular necrosis during the intervention periods (3 periods of 6 months each: January 1 to June 30 of 2015, 2016, and 2017) were compared to one preintervention period (January 1, 2014, to June 30, 2014). The sample consisted of 269 607 adult hospital discharges, among which there were 39 071 episodes based on laboratory estimates and 27 660 episodes of documented International Classification of Diseases diagnoses of acute kidney injury or acute tubular necrosis. Documented incidence improved significantly from the 2014 preintervention period (5.70%; 95% confidence interval: 5.52%-5.88%) to intervention periods in 2015 (9.89%; 95% confidence interval, 9.66%-10.12%; risk ratio = 1.73, P < .001), 2016 (12.76%; 95% confidence interval, 12.51%-13.01%; risk ratio = 2.24, P < .001), and 2017 (12.49%; 95% confidence interval, 12.24%-12.74%; risk ratio = 2.19, P < .001). A multifactorial intervention comprising daily laboratory alerting and education of physicians, nurses, and clinical documentation improvement specialists led to increased recognition and clinical documentation of acute kidney injury.

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BACKGROUND: Kidney disease is an important extra-hepatic manifestation of hepatitis B virus (HBV) infection. However, there is paucity of recent literature on kidney disease in children and adolescents with HBV infection from several parts of sub-Saharan Africa including Nigeria. OBJECTIVE: To review the pattern of kidney disease in hepatitis B surface antigen (HBsAg)-positive children and adolescents seen at a tertiary hospital in south-west Nigeria. METHODS: A retrospective study was undertaken of HBsAg-seropositive children with kidney disease managed at University College Hospital, Ibadan, from January 2004 to December 2015. Patients were identified from the paediatric nephrology unit admissions and the renal histology registers. RESULTS: 24 children and adolescents were studied, 17 of whom were male (70.8%), and the median age was 10.0 years (range 3-15). Ten (41.7%) had nephrotic syndrome, five (20.8%) had non-nephrotic glomerulonephritis, five (20.8%) were in end-stage renal disease (ESRD), including a patient with posterior urethral valves, and four had acute kidney injury secondary to acute tubular necrosis. Renal histology was available for 10 patients: nine had nephrotic syndrome associated with minimal change disease in six, focal segmental glomerulosclerosis in two and one had membanoproliferative glomerulonephritis. The patient with non-nephrotic glomerulonephritis had diffuse global sclerosis. CONCLUSION: The pattern of kidney disease in HBV-positive children demonstrated a predominance of nephrotic syndrome, followed by non-nephrotic glomerulonephritis, ESRD and acute kidney injury. Better diagnostic facilities and treatment are required. Prevention of HBV infection by universal childhood immunisation is the ultimate goal.

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Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m2/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.

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BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality, morbidity, hospital length of stay, and costs. A quantitative urine test is available to assess the risk of developing AKI by measuring the concentrations of two protein biomarkers, TIMP-2 and IGFBP-7. The NephroCheck Test combines these concentrations into an AKIRisk Score. The purpose of this study is to characterize the analytical performance characteristics of the AKIRisk Score. METHODS: Linearity and analytical sensitivity were evaluated by following Clinical Laboratory Standards Institute (CLSI) EP06-A and EP17-A, respectively. Precision was evaluated by testing clinical samples and examining the repeatability of test results. Potential interference was evaluated for endogenous and exogenous substances. Sample stability was examined at room temperature and at 2-8°C, as well as the effect of sample centrifugation temperature on test results. RESULTS: The AKIRisk Score exhibits approximately 10% coefficient of variation (CV) at the recommended cutoff value of 0.3 and the limit of quantitation (LoQ) was 0.002. Only albumin, bilirubin (conjugated), and methylene blue interfered with test results, at concentrations exceeding 1250 mg/L, 72 mg/L, and 0.49 mg/L, respectively. AKIRisk Score results were stable for 6h at room temperature, 24h refrigerated, and not impacted by sample centrifugation temperature. CONCLUSIONS: Our studies demonstrate that the AKIRisk Score has robust analytical performance, good precision, minimal analytical interference, acceptable sensitivity, and excellent sample stability.

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BACKGROUND: The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guidelines establish international recommendations for the definition and treatment of kidney disease. Our objective was to characterize the strength of evidence supporting the KDIGO guidelines, the class of recommendations made, and the relationship between these. STUDY DESIGN: We reviewed and abstracted the level of evidence and strength of recommendations in the currently available KDIGO guidelines. SETTING & POPULATION: KDIGO clinical practice guidelines target care of patients with kidney disease to improve outcomes. SELECTION CRITERIA FOR STUDIES: All KDIGO guidelines published on the KDIGO website as of November 2013 were included. PREDICTOR: Recommendations pertaining to disease, diagnosis, or treatment. OUTCOMES: Levels of evidence and strength of recommendations. RESULTS: Of 853 recommendations in 9 guidelines, 5% were supported by level A quality evidence; 17%, level B; 31%, level C; 18%, level D; and 20%, ungraded evidence. The strength of recommendations was class 1 for 25%, class 2 for 54%, and ungraded for 20%. Only 3% of recommendations were class 1 in strength and supported by level A evidence. Of the recommendations, 2% concerned disease definition and classification; 29%, diagnosis; and 69%, treatment. LIMITATIONS: Our study included only the KDIGO guidelines. We did not assess historical changes in nephrology guidelines recommendations. CONCLUSIONS: KDIGO recommendations were based largely on weak evidence, reflecting expert opinion. Few recommendations were both strong and supported by high-level evidence.

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The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.

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The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.

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OBJECTIVE: There are many kidney transplant recipients and living donors of reproductive age, and the prevalence of pregnancies in kidney transplant recipients can reach 55% in the Middle Eastern countries. Living kidney donation is predominant in this region. As the risks and outcomes of pregnancy should be a part of counselling for both recipients and donors, we reviewed available reports on maternal and foetal outcomes in these particular populations. METHODS: Information was obtained from retrospective analyses of a large database, and from single-centre reports indexed in PubMed on pregnancy in donors and kidney transplant recipients. The keywords used for the search included 'fertility', 'kidney disease', 'pregnancy', 'maternal/foetal outcomes', 'kidney transplant recipient', 'immunosuppression side-effects', 'living donor' and 'Arab countries'. RESULTS: Pregnancies in kidney transplant recipients are most successful in those with adequate kidney function and controlled comorbidities. Similarly to other regions, pregnant recipients in the Middle East had a higher risk of pre-eclampsia (26%) and gestational diabetes (7%) than in the general population. Caesarean section was quite common, with an incidence rate of 61%, and the incidence of pre-term birth reached 46%. CONCLUSIONS: Most living donors can have successful pregnancies and should not be routinely discouraged. Women who had pregnancies before and after donation were more likely to have adverse maternal outcomes (gestational diabetes, hypertension, proteinuria, and pre-eclampsia) in the latter, but no adverse foetal outcomes were found after donation. The evaluation before donation should include a gestational history and counselling about the potential risks.