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.

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.

Charitable medication distribution improves care for uninsured patients with diabetes.

OBJECTIVES: This study examined the impact of insulin products donated by a pharmaceutical manufacturer and dispensed by Dispensary of Hope-partnered pharmacies on medication access and treatment outcomes among uninsured patients with type 2 diabetes (T2D). STUDY DESIGN: This was a pilot, single-center, retrospective observational study. METHODS: Uninsured patients with diabetes who were newly established with Ascension Medical Group clinics for the treatment of T2D were included in this study. Participants were prescribed insulin glargine, insulin isophane, or insulin isophane/insulin regular insulin therapy between March 2020 and August 2021. A retrospective chart review was conducted. Information collected included participants' hemoglobin A1c (HbA1c) level at baseline, 3 months, and 6 months; change in HbA1c level; insulin prescribed; fill history; whether they had been referred to a patient assistance program; and whether they were seen by a pharmacist under a collaborative practice agreement. RESULTS: Thirty-eight participants were assessed, and 22 met criteria for the primary outcome. The mean HbA1c level decreased from 11.2% at baseline to 8.9% at 3 months and 8.8% at 6 months, resulting in a mean change in HbA1c of -2.4 percentage points (P = .033). Eleven participants (50%) had an HbA1c level of less than 9% at 6 months. The mean proportion of days covered was 76%. The mean monthly savings for insulin ranged from $183.74 (insulin isophane) to $253.84 (insulin glargine) per participant. CONCLUSIONS: Our results showed a significant improvement in glycemic control among participants, demonstrating the substantial impact that pharmacies partnered with charitable medication distributors such as the Dispensary of Hope can have on individuals with insulin-treated T2D.

Exploring biopsychosocial correlates of pregnancy risk and pregnancy intention in women with chronic kidney disease.

INTRODUCTION: Women with Chronic Kidney Disease (CKD) are at increased risk of adverse pregnancy and renal outcomes. It is unknown how women with CKD understand their pregnancy risk. This nine-centre, cross-sectional study aimed to explore how women with CKD perceive their pregnancy risk and its impact on pregnancy intention, and identify associations between biopsychosocial factors and perception of pregnancy risk and intention. METHODS: Women with CKD in the UK completed an online survey measuring their pregnancy preferences; perceived CKD severity; perception of pregnancy risk; pregnancy intention; distress; social support; illness perceptions and quality of life. Clinical data were extracted from local databases. Multivariable regression analyses were performed. Trial registration: NCT04370769. RESULTS: Three hundred fifteen women participated, with a median estimated glomerular filtration rate (eGFR) of 64 ml/min/1.73m2 (IQR 56). Pregnancy was important or very important in 234 (74%) women. Only 108 (34%) had attended pre-pregnancy counselling. After adjustment, there was no association between clinical characteristics and women's perceived pregnancy risk nor pregnancy intention. Women's perceived severity of their CKD and attending pre-pregnancy counselling were independent predictors of perceived pregnancy risk. Importance of pregnancy was an independent predictor of pregnancy intention but there was no correlation between perceived pregnancy risk and pregnancy intention (r = - 0.002, 95% CI - 0.12 to 0.11). DISCUSSION: Known clinical predictors of pregnancy risk for women with CKD were not associated with women's perceived pregnancy risk nor pregnancy intention. Importance of pregnancy in women with CKD is high, and influences pregnancy intention, whereas perception of pregnancy risk does not.

Renal biopsy findings among Indigenous Australians: a nationwide review.

Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS.

APOL1 genotypes: Do they contribute to ethnicity-associated biological health inequalities in pregnancy?

Inferior health outcomes for people of African and Afro-Caribbean ancestry compared to those of European ancestry are well recognised. There is a disproportionate impact within these communities compared to other ethnic groups including pregnancy outcomes, hypertension, kidney disease and diabetes. The 'Black Lives Matter' movement has highlighted that it is imperative to examine all factors contributing to this inequity and to strive to explore multifaceted ways, including social, economic, psychological and biological to improve overall health equity. It is within this context that we discuss the novel finding of Apolipoprotein 1 genetic polymorphisms which have been identified in some populations of African ancestry. We will explore the history and evolutionary advantages of Apolipoprotein 1 polymorphisms and the pathophysiology resulting from these adaptations and examine the impact of Apolipoprotein 1 on pregnancy outcomes, the risks and benefits of screening for high-risk Apolipoprotein 1 alleles in black communities and potential treatments currently being investigated.

Perceptions of risk in pregnancy with chronic disease: A systematic review and thematic synthesis.

BACKGROUND: Women with chronic disease are at increased risk of adverse pregnancy outcomes. Pregnancies which pose higher risk, often require increased medical supervision and intervention. How women perceive their pregnancy risk and its impact on health behaviour is poorly understood. The aim of this systematic review of qualitative literature is to evaluate risk perceptions of pregnancy in women with chronic disease. METHODS: Eleven electronic databases including grey literature were systematically searched for qualitative studies published in English which reported on pregnancy, risk perception and chronic disease. Full texts were reviewed by two researchers, independently. Quality was assessed using the Critical Appraisal Skills Programme Qualitative checklist and data were synthesised using a thematic synthesis approach. The analysis used all text under the findings or results section from each included paper as data. The protocol was registered with PROSPERO. RESULTS: Eight studies were included in the review. Three themes with sub-themes were constructed from the analysis including: Information Synthesis (Sub-themes: Risk to Self and Risk to Baby), Psychosocial Factors (Sub-themes: Emotional Response, Self-efficacy, Healthcare Relationship), and Impact on Behaviour (Sub-themes: Perceived Risk and Objective Risk). Themes fitted within an overarching concept of Balancing Act. The themes together inter-relate to understand how women with chronic disease perceive their risk in pregnancy. CONCLUSIONS: Women's pregnancy-related behaviour and engagement with healthcare services appear to be influenced by their perception of pregnancy risk. Women with chronic disease have risk perceptions which are highly individualised. Assessment and communication of women's pregnancy risk should consider their own understanding and perception of risk. Different chronic diseases introduce diverse pregnancy risks and further research is needed to understand women's risk perceptions in specific chronic diseases.

CKD in Aboriginal Australians.

Chronic kidney disease (CKD) is one component of a spectrum of chronic disease in Aboriginal Australians. CKD is marked by albuminuria, which predicts renal failure and nonrenal natural death. Rates vary greatly by community and region and are much higher in remote areas. This reflects the heterogeneous characteristics and circumstances of Aboriginal people. CKD is multideterminant, and early-life influences (notably low birth weight), infections (including poststreptococcal glomerulonephritis), metabolic/hemodynamic parameters, and epigenetic/genetic factors probably contribute. CKD is associated intimately with cardiovascular risk. Albuminuria progresses over time, with a high incidence of new onset of pathologic levels of albuminuria in all age groups. All the usual morphologic findings are found in renal biopsy specimens. However, glomerular enlargement is notable in individuals from remote regions, but not those living closer to population centers. Glomerulomegaly probably represents compensatory hypertrophy caused by low nephron number, which probably underlies the accentuated susceptibility to renal disease. In the last decade, health care services have been transformed to accommodate systematic chronic disease surveillance and management. After a relentless increase for 3 decades, rates of Aboriginal people starting renal replacement therapy, as well as chronic disease deaths, appear to be stabilizing in some regions. Official endorsement of these system changes, plus ongoing reductions in the incidence of low birth weight and infections, hold promise for continued better outcomes.

Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is progressive, resulting in end-stage kidney failure in most patients. Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically. MATERIAL AND METHODS: This randomized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD. Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years. Trial visits were conducted every 3 months, assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion. RESULTS: There were no significant (p > 0.05) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients (p = 0.029). CONCLUSION: This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD. The lack of statistical power limits the external validity of these findings. A larger, longer duration study using a higher dose of a more potent statin is required.

The investigation of hematuria.

Persistent microscopic hematuria is present in about 6% of the population, but probably only a small minority have hematuria that does not originate from the glomerulus. Careful analysis of phase-contrast urine microscopy by a skilled observer is critically important in the investigation of hematuria. In glomerular disease, urine microscopy often is second only to renal biopsy examination in helping make a diagnosis. Glomerular and nonglomerular hematuria are distinguished easily on phase-contrast urine microscopy or by an automated peripheral blood cell counter. However, urine microscopy provides additional information about casts and other features that may enable such disparate diagnoses as Fabry's disease, sickle cell disease, and cystine calculi to be made. Macroscopic nonglomerular hematuria is of particular significance because it is much more likely than microscopic hematuria to be associated with malignancy. Macroscopic hematuria originating from the glomerulus indicates the presence of crescentic disease, which requires urgent assessment by renal biopsy examination. We advocate a renal biopsy examination in any individual with a persisting urinary erythrocyte count greater than 100,000/mL. Thirty percent of patients with isolated microscopic hematuria have mesangial immunoglobulin A glomerulonephritis (IgAN) shown on biopsy examination and 20% to 40% of these patients will progress to renal failure without treatment.

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Hypothesis: obesity and the insulin resistance syndrome play a major role in end-stage renal failure attributed to hypertension and labelled 'hypertensive nephrosclerosis'.

About a third of new cases of renal failure in USA are attributed to hypertension despite controversy about the frequency and pathology of so called hypertensive nephrosclerosis. In spite of good documentation that obesity causes renal failure and in spite of the global epidemic of obesity this diagnosis does not feature on most renal failure registries. New documentation that progressive renal failure in hypertension is linked to insulin resistance and analysis of NHANES III data which shows a strong positive significant dose-response relationship between insulin resistance and chronic kidney disease strengthen the view that so called hypertensive nephrosclerosis may be linked more closely to obesity and insulin resistance than to blood pressure. The pathology of the kidney in hypertension has changed. Studies 50 years ago did not show segmental glomerulosclerosis, which has recently been shown to be the key lesion in hypertensive nephrosclerosis. Recent documentation that this is a major mechanism of progression in hypertension together with the fact that similar segmental glomerulosclerosis is the key lesion in obesity and the metabolic syndrome suggests that these factors are more important than hypertension in renal failure attributed to hypertensive nephrosclerosis.

Reduction of proteinuria by rosiglitazone in non-diabetic renal disease.

AIM: To investigate the effect of a thiazolidinedione on proteinuria in patients with non-diabetic renal disease. METHODS: In an open-label randomized cross-over study, 40 adults with chronic non-diabetic renal disease completed the study. In a random fashion, one group was treated for 4 months with 4 mg of rosiglitazone first followed by a 4-month period of standard treatment. The opposite order was used for the second group. RESULTS: Baseline urinary protein excretion rate was 1.45 g/24 h. On rosiglitazone, there was a drop of urinary protein level of 0.24 g/24 h (P=0.045). In contrast, there was a trend for proteinuria to increase during the control period (0.12 g/24 h, P=0.18). The urine protein level on rosiglitazone was lower than on usual treatment (0.36 g/24 h, P=0.002, 95% CI 0.15-0.58). There was a similar beneficial effect on systolic blood pressure which was reduced by rosiglitazone by 7.8 mmHg (P=0.006, 95% CI 2.6-13.1). Although average fasting glucose was only 5.8 mmol/L, there was a significant Spearman correlation between fasting glucose and a reduction in urinary protein levels (r=0.34, P=0.045). CONCLUSION: It is concluded that thiazolidinediones may have a role in the management of non-diabetic proteinuria of various aetiologies. In this study the average body mass index was 28.9 kg/m2. It will be important to repeat these studies in non-overweight subjects with non-diabetic proteinuria and in addition to trial maximal therapeutic doses of the thiazolidenedione.

Pharmacological management of membranous nephropathy.

When steroids and immunosuppressive drugs were the only available pharmacological agents used to treat membranous nephropathy, nephrologists were polarized into two groups, those supporting therapy on the basis of the results achieved in controlled trials and those opposed to therapy who contended that the side-effects of therapy were too severe to consider in a disease with a relatively benign course. These two groups are drawing closer as treatments with lesser side-effects emerge. The demonstration that proteinuria accelerates progressive kidney failure in all renal diseases led to a major focus on control of proteinuria. Angiotensin-converting enzyme inhibitors, diuretics and angiotensin II receptor antagonists all play a role. Older methods of treatment that reduce proteinuria are being resurrected. A major development is the demonstration in a randomized study that cyclosporin A is effective in membranous nephropathy. Therefore, although there has been no major recent breakthrough or novel therapeutic agent used in membranous nephropathy, a range of new methods of controlling proteinuria provide some compromise between therapeutic enthusiasm and conservative management in this common disorder.

The fifth freedom.

Women in developing countries suffer considerable morbidity and mortality due to inability to control their own fertility and lack of access to family planning services. Over 500,000 deaths each year are related to pregnancy. Two thirds of these maternal deaths could be prevented by providing contraception to those women who wish to use it in developing countries. There is no tenable ethical defence of cultural and religious behaviour which denies a women a choice as to whether she will undertake a pregnancy or not. Implementaion of the principles of the programme of action from the 1994 Cairo Population Conference would, through empowering women to control their own fertility, have a huge impact on maternal health in the developing world. [Kincaid-Smith is president of the World Medical Association].

Randomized controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proteinuria.

BACKGROUND: Proteinuria and hypertension have independent deleterious effects on the progression of chronic renal disease. The objectives of this study were to determine whether the addition of Candesartan, an angiotensin II receptor antagonist, would reduce proteinuria and blood pressure in normotensive patients with chronic renal disease already receiving an angiotensin converting enzyme inhibitor (ACEI). METHODS: This was an open randomized controlled crossover study conducted in a private consultant practice in Melbourne. Sixty patients, aged 23-75, who had chronic renal disease and stable proteinuria over 0.5 g in 24 h and were receiving an ACEI, were enrolled in the study. The patients were randomized to have 8 mg of Candesartan added in the first or second of two 12-week study periods. The primary end point was urine protein excretion, which was measured every 2 weeks for the 24-week period. Secondary end points included systolic and diastolic blood pressure, serum creatinine, urea and potassium levels. Candesartan was added against a background of standard care, which included other blood pressure lowering therapy. RESULTS: Lower urine protein excretion 2.4 vs 2.0 g in 24 h (P<0.04, difference 0.45, CI 0.01, 0.9) and lower levels of systolic blood pressure 134 vs 128 mmHg (P<0.001, difference 6.4, CI 3.2, 9.6) and diastolic blood pressure 82 vs 80 mmHg (P<0.008, difference 2.7, CI 0.7, 4.6) were observed when Candesartan, 8 mg, was added to a regimen, which included an ACEI. No rise in serum creatinine occurred but there was a significant rise in urea, during the Candesartan arm of the study, from 12.3 to 13.8 mmol/l (P<0.001). The addition of 8 mg of Candesartan in normotensive patients with chronic renal disease receiving ACEI appeared safe and was not accompanied by adverse effects apart from postural hypotension in three patients and a serum potassium level of 6.3 mmol/l in one. CONCLUSIONS: In a private consulting practice setting, the addition of 8 mg of Candesartan in normotensive patients with chronic renal disease and proteinuria receiving an ACEI reduced proteinuria and blood pressure. The combination of Candesartan and ACEI appeared safe in this setting and may offer additional protection in preventing progression in chronic renal disease. Although the reduction of proteinuria was small (0.45 g/24 h) this reflected in part a lack of response in diabetic nephropathy and in part a marked rise in proteinuria after ceasing Candesartan in patients who did not complete the Candesartan arm of the study.