Performance and pitfalls of the tools for measuring glomerular filtration rate to guide chronic kidney disease diagnosis and assessment.

Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio (UACR) and the kidney failure risk equation (KFRE) are important tools to achieve this, but understanding their limitations is important for optimal implementation.When accurate GFR is required (eg, chemotherapy dosing), GFR is measured using an exogenous filtration marker. In routine clinical practice, in contrast, estimated GFR (eGFR) from serum creatinine (SCr), calculated using the enzymatic method±UACR, is recommended. Limitations of SCr include non-GFR determinants such as muscle mass, diet and tubular handling. An alternative or additional endogenous filtration marker is cystatin C, which can be used alongside SCr for confirmatory testing of CKD. However, its role in the UK is more limited due to concerns regarding false positive results.The recommended creatinine-based eGFR equation in the UK is the CKD Epidemiology Collaboration 2009 equation. This was recently updated to a race-neutral 2021 version and demonstrated reduced bias in people of Black ethnicity, but has not been validated in the UK. Limitations are extremes of age, inaccuracy at greater GFRs and reduced generalisability to under-represented ethnicity groups.The KFRE (based on age, sex, SCr and UACR) has recently been developed to help determine 2-year and 5-year risk of progression to end-stage kidney disease. It has been validated in over 30 countries and provides meaningful quantitative information to patients. However, supporting evidence for their performance in ethnic minority groups and kidney diseases such as glomerulonephritis remains modest.In conclusion, early identification, risk stratification of kidney disease and timely intervention are important to impact kidney disease progression. However, clinician awareness of the limitations and variability of creatinine, cystatin C and the eGFR equations, is key to appropriate interpretation of results.

Ethnic disparities in pregnancy-related acute kidney injury in a United Kingdom population.

BACKGROUND: The incidence of acute kidney injury in pregnancy (P-AKI) is rising and is associated with detrimental maternal and foetal outcomes. Ethnic disparities in pregnancy outcomes are well recognized, with females who identify as Black or Asian being more likely to die during pregnancy compared to females who identify as White ethnicity. METHODS: This study reports rates of P-AKI and associated risk factors in pregnant females of different ethnicities. All pregnancies were recorded between 2016 and 2020. AKI episodes were identified using electronic alerts. Ethnicity, AKI stage (1-3), obstetric outcomes and risk factors for P-AKI (chronic hypertension, pregnancy-induced hypertension and pre-eclampsia, and haemorrhage) were assessed. RESULTS: There were 649 P-AKI episodes from 16,943 deliveries (3.8%). Black females were more likely to have P-AKI (5.72%) compared to those who were White (3.12%), Asian (3.74%), mixed ethnicity (2.89%) and Other/Not Stated (3.10%). Black females, compared to White females, were at greater risk of developing P-AKI if they had haemorrhage requiring blood transfusion (OR 2.44, 95% CI 1.31,4.54; p < 0.001) or pregnancy-induced hypertension (OR 1.79, 95% CI 1.12, 2.86; p < 0.001). After adjusting for risk factors, Black females had increased risk of developing P-AKI (OR 1.52, 95% CI 1.22, 1.80; p < 0.001) compared to White females. Black females were at increased risk of developing P-AKI compared to White females. Mode of delivery, pregnancy-induced hypertension and haemorrhage are likely to have contributed. The increased risk persists despite accounting for these variables, suggesting that other factors such as socioeconomic disparities need to be considered. CONCLUSIONS: The incidence of P-AKI is likely higher than previously stated in the literature. However, caution must be exercised, particularly with AKI stage 1, as the KDIGO system is not validated in pregnancy and gestational changes in renal physiology need to be considered. Pregnancy-specific AKI definitions are needed.

Systematic review of pregnancy and renal outcomes for women with chronic kidney disease receiving assisted reproductive therapy.

BACKGROUND: As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our aim was to perform a systematic review to describe obstetric and renal outcomes in women with CKD following ART. METHODS: The following databases were searched from 1946 to May 2021: (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) Embase and (4) MEDLINE. RESULTS: The database search identified 3520 records, of which 32 publications were suitable. A total of 84 fertility treatment cycles were analysed in 68 women. Median age at time of pregnancy was 32.5 years (IQR 30.0, 33.9 years). There were 60 clinical pregnancies resulting in 70 live births (including 16 multifetal births). Four women developed ovarian hyperstimulation syndrome which were associated with acute kidney injury. Hypertensive disorders complicated 26 pregnancies (38.3%), 24 (35.3%) pregnancies were preterm delivery, and low birth weight was present in 42.6% of pregnancies. Rates of live birth and miscarriage were similar for women with CKD requiring ART or having natural conception. However, more women with ART developed pre-eclampsia (p < 0.05) and had multifetal deliveries (p < 0.001), furthermore the babies were lower gestational ages (p < 0.001) and had lower birth weights (p < 0.001). CONCLUSION: This systematic review represents the most comprehensive assessment of fertility outcomes in patients with CKD following ART. However, the high reported live birth rate is likely related to reporting bias. Patient selection remains crucial in order to maximise patient safety, screen for adverse events and optimise fertility outcomes.

Hyperkalemia in Chronic Kidney Disease: Links, Risks and Management.

Hyperkalemia is a common clinical problem with potentially fatal consequences. The prevalence of hyperkalemia is increasing, partially due to wide-scale utilization of prognostically beneficial medications that inhibit the renin-angiotensin-aldosterone-system (RAASi). Chronic kidney disease (CKD) is one of the multitude of risk factors for and associations with hyperkalemia. Reductions in urinary potassium excretion that occur in CKD can lead to an inability to maintain potassium homeostasis. In CKD patients, there are a variety of strategies to tackle acute and chronic hyperkalemia, including protecting myocardium from arrhythmias, shifting potassium into cells, increasing potassium excretion from the body, addressing dietary intake and treating associated conditions, which may exacerbate problems such as metabolic acidosis. The evidence base is variable but has recently been supplemented with the discovery of novel oral potassium binders, which have shown promise and efficacy in studies. Their use is likely to become widespread and offers another tool to the clinician treating hyperkalemia. Our review article provides an overview of hyperkalemia in CKD patients, including an exploration of relevant guidelines and nuances around management.

Fludrocortisone Is an Effective Treatment for Hyperkalaemic Metabolic Acidosis in Kidney Transplant Recipients on Tacrolimus: A Case Series.

BACKGROUND: Hyperkalaemia with metabolic acidosis is common but under-reported following kidney transplantation. Calcineurin inhibitors, such as tacrolimus, are widely used in the management of transplant patients and are associated with the development of hyperkalaemia. We report on 10 renal transplant patients, treated with fludrocortisone, following identification of hyperkalaemic metabolic acidosis. RESULTS: All 10 patients were male aged (mean ± SD) 53.0 ± 13.2 years; 7 were Caucasian and 3 South Asian. Before and after fludrocortisone administration, respective (mean ± SD) serum potassium was 6.1 ± 0.4 mmol/L and 5.3 ± 0.3 mmol/L (p = 0.0002); serum bicarbonate 18.5 ± 1.6 mmol/L and 20.5 ± 2.3 mmol/L (p = 0.002); serum sodium 135 ± 4.6 mmol/L and 137 ± 2.2 mmol/L (p = 0.0728); serum creatinine 181 ± 61 µmol/L and 168 ± 64 µmol/L (p = 0.1318); eGFR 42 ± 18 mL/min and 46 ± 18 mL/min (p = 0.0303); blood tacrolimus 10.1 ± 2.9 ng/mL and 10.4 ± 1.4 ng/mL (p = 0.7975); and blood pressure 129 ± 15/79 ± 25 mm Hg and 126 ± 24/75 ± 7 mm Hg. Pre-fludrocortisone, there were 7 episodes of serum potassium ≥6.5 mEq/L, with 4 patients requiring admission for the treatment of hyperkalaemia. Following fludrocortisone, no patients had hyperkalaemia requiring inpatient management. CONCLUSIONS: Treatment of hyperkalaemic metabolic acidosis in transplant patients on tacrolimus with low-dose fludrocortisone resulted in rapid correction of hyperkalaemia and acidosis without significant effects on blood pressure or serum sodium. Fludrocortisone can be an effective short-term option for the treatment of hyperkalaemic metabolic acidosis in kidney transplant recipients on tacrolimus; however, patient selection remains important in order to reduce to risk of potential adverse effects.

Estimated glomerular filtration rate equations in people of self-reported black ethnicity in the United Kingdom: Inappropriate adjustment for ethnicity may lead to reduced access to care.

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin <30g/l, liver disease, <18 years, of non-Black or non-White self-reported ethnicity were excluded. Agreement was assessed by bias, precision and 30%-accuracy and was stratified for ethnicity and GFR. 1888 51Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m2 respectively, p<0.001). Disregarding the ethnicity adjustment significantly improved GFR estimates for Black participants (bias 6.7 and 2.4ml/min/1.73m2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p<0.001). The LM Revised equation had the smallest bias for both White and Black participants (5.8ml and -1.1ml/min/1.73m2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m2 compared to <60ml/min/1.73m2 using eGFR-CKD-EPI equation for both White and Black participants (p<0.001). Multivariate regression methodology with adjustment for age, sex and log(serum creatinine) in the cohort yielded an ethnicity coefficient of 1.018 (95% CI: 1.009-1.027). Overestimation of measured GFR with eGFR equations using ethnicity adjustment factors may lead to reduced CKD diagnosis and under-recognition of severity in people of Black ethnicity. Our findings suggest that ethnicity adjustment for GFR estimation in non-African Americans may not be appropriate for use in people of Black ethnicity in the UK.

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.

Hypergonadotrophic hypogonadism due to testicular adrenal rest tumours presenting with hypogonadotrophic hypergonadism.

Primary testicular failure is characterized by low serum testosterone with appropriately high serum gonadotrophins, that is hypergonadotrophic hypogonadism. We report on a 27-year-old man with congenital adrenal hyperplasia (CAH) and infertility due to testicular adrenal rest rumours (TART) resulting in primary testicular failure but presenting with azoospermia, elevated serum testosterone and very low serum gonadotrophins. Hypergonadotrophic hypogonadism was unmasked by increasing glucocorticoid dosage. It is important to recognise the limitations of follicle-stimulating hormone, luteinising hormone and testosterone in assessing testicular function in men with CAH. Abnormal semen analysis may be the best indicator of testicular dysfunction in men with CAH.