COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort.

BACKGROUND: Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. METHODS: We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. RESULTS: Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24-4,18; p <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27-2.53; p <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19-2.13) for stage 1; p < 0.005, 2.71(95%CI 1.82-4.05); p < 0.001for stage 2 and 2.99 (95%CI 2.17-4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. CONCLUSIONS: This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3-6 months.

Acute Peritoneal Dialysis With Percutaneous Catheter Insertion for COVID-19-Associated Acute Kidney Injury in Intensive Care: Experience From a UK Tertiary Center.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, high rates of acute kidney injury (AKI) in critically unwell patients are being reported, leading to an increased demand for renal replacement therapy (RRT). Providing RRT for this large number of patients is proving challenging, and so alternatives to continuous renal replacement therapies (CRRT) in the intensive care unit (ICU) are needed. Peritoneal dialysis (PD) can be initiated immediately after percutaneous insertion of the catheter, but there are concerns about impact on ventilation and RRT efficacy. We sought to describe our recent experience with percutaneous catheter insertion and peritoneal dialysis in patients in the ICU with COVID-19 infection. METHOD: Patients were selected according to local protocol, and catheters were inserted percutaneously by experienced operators using a Seldinger technique. Sequential Organ Failure Assessment (SOFA) score and ventilation requirements were recorded at the time of insertion and 24 hours later. Procedural complications, proportion of RRT provided by PD, renal recovery, and RRT parameters (serum potassium and maximum base excess) during PD were assessed. RESULTS: Percutaneous PD catheters were successfully inserted in 37 of 44 patients (84.1%) after a median of 13.5 days (interquartile range [IQR] = 10.0, 20.3 days) in the ICU. No adverse events were reported; SOFA scores and ventilation requirements were comparable before and after insertion; and adequate RRT parameters were achieved. The median proportion of RRT provided by PD following catheter insertion was 94.6% (IQR = 75.0, 100%). CONCLUSION: Peritoneal dialysis provides a safe and effective alternative to CRRT in selected patients with AKI and COVID-19 infection requiring ventilation on intensive care.

Acute kidney injury e-alerts in pregnancy: rates, recognition and recovery.

BACKGROUND: Acute kidney injury (AKI) in pregnancy (Pr-AKI) is associated with substantial maternal morbidity and mortality. E-alerts are routinely used for detection of AKI in non-pregnant patients but their role in maternity care has not been explored. METHODS: All pregnant or postpartum women with AKI e-alerts for AKI Stages 1-3 (Kidney Disease Improving Global Outcomes (KDIGO) criteria) were identified at a tertiary centre >2 years. Two women matched by delivery date for each case were selected as controls. AKI stage, recognition of AKI, pregnancy outcomes, renal recovery, AKI aetiology and risk factors were extracted from electronic patient records. RESULTS: 288 of 11 922 (2.4%) women had AKI e-alerts, of which only 118 (41%) were recognized by the obstetric team. Common Pr-AKI causes included infection (48%), pre-eclampsia (26%) and haemorrhage (25%), but no cause was identified in 15% of women. Renal function recovered in 213 (74%) women, but in 47 (17%) repeat testing was not undertaken and 28 (10%) did not recover function. Hypertensive disorders of pregnancy and Caesarean section were associated with increased incidence of Pr-AKI compared with controls. CONCLUSIONS: Pr-AKI e-alerts were identified in ∼1 in 40 pregnancies. However, a cause for Pr-AKI was not identified in many cases and e-alerts may have been triggered by gestational change in serum creatinine. Pregnancy-specific e-alert algorithms may be required. However, 1 in 10 women with Pr-AKI had not recovered kidney function on repeat testing. Better understanding of long-term impacts of Pr-AKI on pregnancy and renal outcomes is needed to inform relevant Pr-AKI e-alert thresholds.

A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment.

Acute kidney injury (AKI) is a common presentation which can result from a number of different underlying pathological processes. Haematological malignancies, particularly multiple myeloma (MM), are known to frequently present with AKI. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare condition which can cause crescentic glomerulonephritis (GN), resulting in AKI. We present the case of a 60-year-old man who presented with clinical features suggestive of AAV in the context of blood tests which demonstrated AKI and positive perinuclear ANCA (p-ANCA) and anti-myeloperoxidase (anti-MPO) titres. Further investigations demonstrated an underlying diagnosis of MM. A renal biopsy was ultimately required to determine the cause of AKI, a cast nephropathy. This case is the first to our knowledge which demonstrates a rare situation in which myeloma kidney is associated with positive p-ANCA and anti-MPO titres, without any evidence of a crescentic GN. It highlights the importance of following up on all investigations sent in the context of AKI, even when a potential diagnosis seems evident. Furthermore, it demonstrates the role of renal biopsy in confirming a diagnosis in the context of AKI with multiple differential diagnoses.

Obesity and recovery from acute kidney injury (Ob AKI): a prospective cohort feasibility study.

OBJECTIVES: To test the methodology of recruitment, retention and data completeness in a prospective cohort recruited after a hospitalised episode of acute kidney injury (AKI), to inform a future prospective cohort study examining the effect of obesity on AKI outcomes. DESIGN: Feasibility study. SETTING: Single centre, multi-site UK tertiary hospital. PARTICIPANTS: 101 participants (67M; 34F) with a median age of 64 (IQR 53-73) years, with and without obesity, recruited within 3 months of a hospitalised episode of AKI. OUTCOME MEASURES: Feasibility outcomes were recruitment (>15% meeting inclusion criteria recruited), participant retention at 6 and 12 months (≥80%) and completeness of data collection. Exploratory measures included recovery from AKI (regaining >75% of pre-AKI estimated glomerular filtration rate [eGFR]) at 6 months, development or progression of chronic kidney disease (CKD) (kidney function decrease of ≥25% + rise in CKD category) at 12 months, and associations with poorer kidney outcomes. RESULTS: 41% of eligible patients consented to take part, exceeding the target recruitment uptake rate of 15%. Retention was 86% at 6 months and 78% at 12 months; 10 patients died and three commenced dialysis during the study. Data were 90%-100% complete. Median BMI was 27.9 kg/m2 (range 18.1 kg/m2-54.3 kg/m2). 50% of the cohort had stage 3 AKI and 49% had pre-existing CKD. 46% of the cohort met the AKI recovery definition at 6 months. At 12 months, 20/51 patients developed CKD (39%) and CKD progression occurred in 11/49 patients (22%). Post-AKI interleukin-6 and cystatin-C were associated with 12 months decline in eGFR. CONCLUSIONS: Feasibility to conduct a long-term observational study addressing AKI outcomes associated with obesity was demonstrated. A fully powered prospective cohort study to examine the relationships between obesity and outcomes of AKI is warranted.

Arterial stiffness is a predictor for acute kidney injury following coronary artery bypass graft surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious postoperative complication of cardiac surgery, an episode of which impacts on patient morbidity and mortality. Pulse wave velocity (PWV; a non-invasive measurement tool to assess arterial stiffness) has been shown to predict kidney disease progression, and cardiovascular and all-cause mortality in patients with chronic kidney disease. We hypothesised that PWV would also predict acute kidney injury in subjects who have undergone non-valve repair elective coronary artery bypass graft (CABG) surgery . METHODS: This was a prospective, observational, exploratory study. PWV was determined with a Vicorder device, together with standard clinical and biochemical parameters. AKI staging was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines. RESULTS: 137 patients were included in the study. 85% were male, and mean age was 66.3 years (SD = 9.7 years). There were 40 episodes (29%) of CSA-AKI. Each 1 unit increase in PWV score was associated with a 1.5 fold greater odds of a CSA-AKI event (p = 0.006(odds ratio = 1.5; confidence interval:1.13-2.10). A 1 unit increase in estimated glomerular filtration rate resulted in an estimated 85% decrease in the odds of developing AKI, each year, men have an odds reduction of 15% of developing AKI compared with females and each 1 year increase in age lowered the odds of developing AKI by 87%. CONCLUSIONS: This pilot exploratory study revealed that PWV, assessed prior to non-valve repair elective CABG surgery, independently predicts CSA-AKI events. PWV is a simple, non-invasive technique that could potentially be used to risk stratify for CSA- AKI following elective cardiac surgery. TRIAL REGISTRATION: ClinTrial.Gov NCT02364427 . Registered 18 February 2015.

Single-centre experience of granulomatous interstitial nephritis-time for a new approach?

Background: Differentiating between renal-limited sarcoidosis and tuberculosis (TB) infection as a cause of granulomatous interstitial nephritis (GIN) can be difficult. This series compares clinical features and response to treatment between the different underlying aetiologies in order to propose a management algorithm for GIN to assist with diagnosis and treatment. Methods: This retrospective study reports on all patients presenting with a histological diagnosis of GIN between 2000 and 2012 at our unit. Results: Twenty-one patients were identified, 57% were male and the mean age was 53 years. Eight cases were associated with sarcoidosis with evidence of extra-renal disease and five with renal-limited sarcoidosis. Five patients had GIN that may have been related to TB infection or to renal-limited sarcoidosis, and three were idiopathic or drug related. All those with sarcoidosis were treated with steroids and renal function, as measured by estimated glomerular filtration rate (eGFR), improved from a mean of 24 mL/min at baseline to 37 mL/min at 1 year. Baseline eGFR was 19 mL/min in those with possible TB infection. Four received steroids as well as anti-TB drugs. Anti-TB therapy was delayed in four patients by a mean of 22 months due to difficulties in diagnosis. Two patients with TB developed end-stage kidney disease and the remaining three patients had a mean eGFR of 28 mL/min at 1 year. Conclusions: This series represents the largest cohort of patients with GIN in the UK and supports previous findings that patients with sarcoid have a favourable outcome with steroid treatment. Those with TB have an inferior prognosis, perhaps due to delayed diagnosis. We suggest an algorithm when investigating a diagnosis of GIN with the aim of expediting diagnosis and considering a trial of anti-TB therapy in order to prevent deterioration of renal function.

Black ethnicity predicts better survival on dialysis despite greater deprivation and co-morbidity: a UK study.

BACKGROUND: Observational studies from the United States have identified black race as conferring a survival advantage on dialysis. This study represents the first large single-center study from a UK dialysis unit examining the outcome of ethnic minorities on renal replacement therapy (RRT). METHODS: A retrospective analysis of all patients of white or black race initiating RRT at King's College Hospital Renal Unit, London, between 1996 and 2008 was performed. A total of 1,340 patients were studied, of which 952 (71%) were of white race, and 388 (29%) were of black race. Kaplan-Meier survival curves, the log rank test and Cox's proportional hazard models were used to compare survival between groups. RESULTS: The results revealed black ethnicity to be associated with a significant survival benefit on dialysis. This was the case even after adjustment for age, gender, diabetes, transplantation, and deprivation. In those patients not transplanted, black race conferred a hazard ratio (HR) of 0.51 (95% CI 0.41 - 0.63) over 5 years. CONCLUSIONS: This study provides evidence for a lower mortality rate amongst black patients on dialysis in comparison with their white counterparts in the UK. The reasons behind this remain poorly understood but a lower incidence of cardiovascular disease in black patients and more kidney-limited disease may be important.

Desmopressin use prior to renal transplant biopsy-does it fit?

Desmopressin acetate (DDAVP), a selective agonist of type 2 vasopressin receptors, is sometimes used prior to percutaneous renal biopsy to reduce the risk of bleeding complications. DDAVP increases free water reabsorption in renal collecting ducts, potentially leading to water intoxication or dilutional hyponatraemia. We present two cases, where DDAVP was used prior to percutaneous renal transplant biopsy and was associated with severe hyponatraemia and neurological sequelae. With DDAVP being advocated in many centres prior to percutaneous renal biopsy, these cases highlight the need for increased awareness regarding side effects. In this report, we provide suggestions on strategies to minimize hyponatraemia in this context.

AA Amyloidosis in a patient with glycogen storage disorder and progressive chronic kidney disease.

Type 1 glycogen storage diseases (GSD) are inherited metabolic diseases caused by defects in the activity of the glucose-6-phosphate transporter. We present the case of a 40-year-old male with glycogen storage disease type 1b (GSD1b) who was referred to our nephrology service for evaluation of his chronic kidney disease and found to have AA amyloid deposition on renal biopsy. Amyloid is a described complication of GSD1b. As the treatment of GSD has improved, patients are surviving longer and are now presenting more frequently to adult services. It is important that clinicians are aware of the possible renal complications of GSD1b.

The incidence of major hemorrhagic complications after renal biopsies in patients with monoclonal gammopathies.

BACKGROUND AND OBJECTIVES: Monoclonal gammopathies frequently cause renal disease, but they may be an incidental finding. Assessment of renal pathology in the context of renal dysfunction and a monoclonal gammopathy therefore serves as a useful diagnostic tool and, in addition, provides prognostic information. There is, however, a theoretical risk of increased hemorrhagic complications from renal biopsies in this setting. The purpose of this study was to determine the incidence of significant hemorrhagic complications after renal biopsies in patients with monoclonal gammopathies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The case notes of 1993 unselected patients from four teaching hospitals within the United Kingdom who underwent native or transplant renal biopsies between 1993 and 2008 were reviewed. Subjects were categorized as having a monoclonal gammopathy or not, and the incidence of major hemorrhagic complications between groups was compared. RESULTS: In total, 74 (3.7%) patients (native and transplant biopsies) had a major hemorrhagic complication. One hundred forty-eight subjects with a monoclonal gammopathy were identified. The complication rate in this group was 4.1% compared with 3.9% in the control population (native biopsies only; P = 0.88). CONCLUSIONS: In the population studied, the rate of major hemorrhagic complications after percutaneous renal biopsy was not significantly greater in patients with a monoclonal gammopathy.

Insights from ambulatory blood pressure monitoring: diagnosis of hypertension and diurnal blood pressure in renal transplant recipients.

BACKGROUND: Accurate diagnosis of hypertension is essential in chronic kidney disease patients, as it is linked to increased left ventricular mass, stroke, cardiovascular mortality and morbidity, and progression to end-stage renal disease. Elevated blood pressure (BP) detected by ambulatory BP monitoring (ABPM) has been shown to be predictive of worse outcome in chronic kidney disease patients. Another predictor of worse outcome is diurnal BP variation, measured also by ABPM. In this study, the authors examined the relationship (concordance or discordance) between blood pressure measured by ABPM compared with daytime office BP, and also explored the predictors of diurnal variation in renal transplant recipients. METHODS: All the patients who underwent renal transplantation and follow-up at the authors' institution from January 1998 to January 2003 were involved in this study (n=177) in addition to another randomly selected 64 patients that underwent transplantation before 1998. All patients had their ABPM performed according to previously described protocols at least 2 weeks after discharge from the hospital, dialysis-independent and with a functioning renal allograft. RESULTS: The authors found a positive correlation between systolic BP (SBP) diurnal variation and age (r =0.263, P <0.0001), glomerular filtration rate (GFR) (r =-0.229, P <0.0001), cyclosporine trough (r =0.171, P =0.047), and ABPM-to-transplant interval (r =-0.133, P =0.039). After fitting a regression model, the authors found that only GFR (P <0.0001) and age (P =0.001) were independent predictors of SBP diurnal variation (r =0.357). Concordance rate between casual BP and ABPM was 80%, and by using casual BP, only 15% of hypertensive renal transplant patients would be erroneously diagnosed as normotensive. CONCLUSIONS: The authors found that SBP diurnal variation is predicted independently by age and GFR, although it does correlate with cyclosporine trough and ABPM-to-transplant interval. In addition, the authors showed that ABPM is a more sensitive method for diagnosing hypertension than is sole reliance on office BP in renal transplant recipients.

Systolic blood pressure diurnal variation is not a predictor of renal target organ damage in kidney transplant recipients.

Elevated blood pressure and diurnal blood pressure variation detected by ambulatory blood pressure monitoring has been shown to be predictive of worse outcome in end-stage renal disease patients in small studies. What has been lacking is a large study to determine whether these ambulatory blood pressure monitoring (ABPM)-derived variables are predictors of worse outcome in renal transplant recipients. All the patients that underwent renal transplantation and follow up at this institution from January 1998 till October 2002 were involved in this study (n=177). All patients were followed up for at least 48 weeks. Last creatinine correlated positively with duration of dialysis (p=0.035, r=0.158), kidney-donor age (p<0.0001, r=0.377), early kidney function (p<0.0001, r=0.610, r=0.683), 24-h systolic blood pressure (SBP) load (p=0.002, r=0.228), and ABPM-derived pulse pressure (p<0.0001, r=0.269). However neither office blood pressure nor SBP diurnal variation were predictors of kidney outcome. Regression analysis showed that early kidney function was the only independent predictor of transplant outcome (p<0.0001). Systolic blood pressure diurnal variation, though an important predictor of target organ damage in chronic kidney disease patients, was not a predictor of renal transplant function in renal transplant recipients. Only early kidney function was an independent predictor of later serum creatinine.